Cancer Research and Medicine (CRM) is an international peer-reviewed open access journal dedicated for original research articles, review papers, case reports, short communications, letters to Editor, meeting reports and special issues on topics identified by the Editorial board. CRM provides platform to the scientific community for sharing latest developments in cancer research. Major areas include carcinogenesis, tumor biology, molecular features, cancer metastasis, screening and diagnosis, biomarkers, chemoprevention, cancer immunology, animal models, anticancer compounds, drug resistance and novel therapeutic targets. The journal supports pre-clinical research including in vitro/ in vivo investigations and clinical findings obtained from cancer patient cohorts. CRM adheres to a double-blind review process and manuscripts are reviewed by at least two referees. CRM is keen for open sharing of the scientific data, fast track review process and broader visibility of the accepted articles. For information on article submission and any other query or help, please visit our support pages: Submission.
Ataxia-Telangiectasia Mutated (ATM) inhibitor induces antineoplastic effects in brain cancer cells: Evidence from in vitro investigations
Background: Brain cancer is a life-threatening disease that originates from abnormal cells growth uncontrollably in brain tissues. Treatment is challenging because of the delicacy of brain and blood–brain barrier which does not allow to enter the medicines easily. Surgery and existing chemotherapeutic measures are helpful but may not destroy all the cancer cells. Thus, there is need for new and more effective medicines to treat brain tumors safely for subsequent improvement and survival. Methods: Human neuroblastoma cells IMR-32 were cultured and exposed with commercially available Ataxia-Telangiectasia Mutated (ATM) inhibitor. Effects on viability of cells were evaluated using a colorimetric assay to determine cytotoxic impact of the treatment. Crystal violet and DAPI staining were performed to monitor cellular growth, nuclear morphology and apoptotic changes in the cells. Gene expression levels were determined using real-time PCR (RT-PCR) to quantify changes in the expression of target genes including apoptosis, cell cycle, stress related markers and transcription factors. Results: Toxicity assay showed reduction in cell viability after treatment with ATM inhibitor. Inhibitory concentration data showed ~7.5µM as the concentration inhibited 50% of the cell viability after 48h exposure. DAPI staining revealed nuclear condensation and fragmentation of DNA content indicating apoptotic changes. Crystal violet staining indicated inhibition of proliferation and colony forming ability of the cells. Apoptosis related genes (CASP3, CASP7, CASP9, BAX, BCL2) were largely induced, while cell cycle (CCND1, CCND2, CDKN1A, CDKN2A, CDKN1B, CDKN2B), stress (GADD34, GADD45A, GADD153) and transcription factors (E2F1, E2F6) were largely inhibited. Conclusion: Exposure with ATM inhibitor restrained the cell proliferation, induced apoptosis, and suppressed colonization. Transcriptomic levels of the genes were altered by ATM inhibitor treatment. The results indicate potential therapeutic value of ATM inhibitor in controlling brain cancer growth and progression.
Copyright (c) 2026 Authors publishing manuscripts with Biology Circle journals agree to transfer copyright to the journal and will grant journal’s right to publication under CC-BY 4.0 license. Authors are strongly encouraged to distribute the published work at their personal levels including social media pages, academic websites and institutional repositories etc. https://creativecommons.org/licenses/by/4.0
In vitro analysis of silkworm sericin induced modifications in migration related genes in colorectal cancer cells
Background: Colorectal cancer is a leading cause of cancer-related deaths worldwide. The search for natural compounds with anticancer activity has gained increasing interest. Sericin, a silk-derived protein, has demonstrated various biological properties, including potential anticancer effects. This study aimed to evaluate anticancer effects of sericin and influence on the expression of genes associated with cancer progression in colorectal cancer cells. Methods: Colorectal cancer cells (SW620, SW480, HCT116) were treated with different concentrations of sericin. Effects on cell viability were monitored and confirmed by MTT assay. The expression levels of focal adhesion kinase (FAK) and Ras-related C3 botulinum toxin substrate (RAC1) genes were analyzed using real-time quantitative polymerase chain reaction. Online data tool (STRING software) was used to assess the protein-protein interactions, biological processes and molecular functions associated with the two genes. Results: Sericin treatment resulted in reduced cellular viability and downregulation of FAK and RAC1 gene expression compared to untreated control cells. The inhibition of these genes indicates suppression of signaling pathways involved in migration and invasion of the colorectal cancer cells. Bioinformatics showed important protein interactors of the genes with the involvement of key biological and molecular functions including growth signaling pathways, secondary messenger networks and kinase activities. Conclusion: The findings suggest that sericin exhibits anticancer activity against colorectal cancer and deregulate the expression of FAK and RAC1 genes. Further in vitro studies are required to investigate the fine cellular tunings to confirm the efficacy.
Comparative cytotoxic analysis of plant synthesized metallic nanoparticles and their extracts against breast cancer cells
Background: Breast cancer remains one of the leading causes of mortality among women worldwide. Several therapeutic strategies including surgery, hormonal therapy, radiotherapy and chemotherapy have been used to fight against cancer. However, these therapies have several drawbacks such as non-specificity, drug resistance, less efficiency and high doses. These disadvantages lead researchers to find therapies which offer more specificity and sensitivity. Among these, plant-based metallic nanoparticles have emerged as a promising approach due to their improved bioactivity and reduced side effects. The present study aimed to evaluate and compare the anticancer potential of aqueous extracts of selected medicinal plants and their corresponding silver (Ag) NPs against the human breast cancer cells. Methods: Aqueous extracts of the plants were prepared, and their AgNPs were synthesized. Cytotoxic effects were assessed using the MTT assay over a concentration range of 0.5–150 µg/ml for both extracts and NPs. Microscopic examination revealed pronounced morphological changes in NP-treated cells compared to those treated with plant extracts only and untreated controls. Results: The MTT assay demonstrated significantly higher cytotoxicity of NPs formulations relative to their respective extracts. The LC50 values of fenugreek-AgNPs, N. sativa-AgNPs, C. colocynthis-AgNPs, A. indica-AgNPs, Z. officinale-AgNPs, and A. sativum-AgNPs were 3.6, 11.2, 4.97, 18, 24.4, and 31.43 µg/ml, respectively. Fenugreek-AgNPs showed the strongest anticancer activity at the lowest concentration. Conclusion: These findings suggest that plant-based NPs exhibit significant anticancer efficacy at lower doses compared to crude plant extracts and may serve as promising candidates for breast cancer therapy.
Anticancer effects of falsa (Grewia asiatica) extracts against breast cancer cells
Background: Breast cancer is the most common cancers among females around the globe. There are treatment options for breast cancer, but with substantial side effects. Low survival rate and advanced stages highlight the need to discover new therapeutic compounds. Purpose of this study was to investigate the effects of Grewia asiatica (falsa) extracts exposure on cell viability and expressional modulation of cell cycle genes (CCND1, CCND2 and CDKN1A) in breast cancer cells. Methods: As a first step, toxic effect of falsa extracts were identified against breast cancer cell line MCF-7. Cell viability was identified by MTT dye reduction assay. Afterwards, expressions of the genes (CCND1, CCND2 and CDKN1A) were identified by real time PCR methodology. Untreated samples were used as controls while the data was analyzed by 2-∆∆CT method to identify fold changes. The difference in fold changes was compared with the untreated controls. Results: The results indicated that the extracts showed moderate anti-proliferative effects against MCF-7 cell line. Real time PCR results showed potential of the fruit extracts to alter expression of genes (CCND1, CCND2 and CDKN1A) in MCF-7. CDKN1A (up to 2.3fold) and CCND1 (up to 1.4fold) genes were upregulated in MCF-7 cells treated with the extracts while CCND2 was downregulated (up to -1.7fold). Conclusion: Falsa extracts induce cell death and alter the expression of cell cycle related genes to halt the growth process in breast cancer cells.
Adipocyte–Tumor Cell Metabolic Communication in the Advancement of Cancer
The tumor-microenvironment (TME) can be defined as an ecosystem comprising various factors including predominantly immunosuppressive cytokines, Tumor-Associated Adipocytes (TAAs) and infiltrating immune cell population (dendritic cells, macrophages, B and T lymphocytes) surrounding a tumor. TME has emerged as a key player in cancer progression, mainly the molecular interaction between tumor cells and its neighboring adipocytes. Adipocyte-derived extracellular vesicles play a pivotal role in cancer invasion by enhancing fatty acid oxidation through the delivery of both fatty acid substrates and essential protein machinery. Interestingly, tumor cells actively induce lipolysis in TAAs promoting the lipolysis that serves as an energy source to fuel tumor growth. Furthermore, the heightened mitochondrial activity in tumor cells leads to the redistribution of mitochondria toward membrane protrusions facilitating cell migration in the presence of adipocyte-derived extracellular vesicles. Collectively, these complex interactions promote cancer cells invasion. Current review provides a comprehensive understanding of the contribution of adipocyte-derived extracellular vesicles in mediating physiological interaction between tumor cells and neighboring adipocytes with a specific emphasis on the tumor advancement.
Copyright (c) 2025 Authors publishing manuscripts with Biology Circle journals agree to transfer copyright to the journal and will grant journal’s right to publication under CC-BY 4.0 license. Authors are strongly encouraged to distribute the published work at their personal levels including social media pages, academic websites and institutional repositories etc. https://creativecommons.org/licenses/by/4.0
Calcium channel blocker (Fendiline) induces cell cycle arrest in pancreatic cancer cells
Background: Pancreatic ductal adenocarcinoma is one of the most lethal malignancies worldwide, characterized by late diagnosis, aggressive progression, and resistance to conventional therapies. The urgent need for novel therapeutic strategies has prompted investigation into drug repurposing approach. Fendiline, a non-selective calcium channel blocker with reported anti-proliferative properties, has emerged as a potential candidate. This study aimed to evaluate its impact on cell cycle progression using flow cytometry. Methods: Human pancreatic cancer cell line (BxPC-3) was treated with increasing concentrations of fendiline (5, 10, 15µM) for the defined time interval (48h). Cell cycle distribution was analyzed by propidium iodide staining followed by flow cytometric quantification of DNA content. Percentage of cells in different phases of the cell cycle were resented in comparison to untreated control. Results: Compared with untreated control cells, fendiline treatment exhibited a marked increase in the G0/G1 population. At the same time, a concomitant reduction in the S phase fraction in response to exposure with drug was noticed. Quantitative analysis demonstrated a dose-dependent effect, with lower concentrations of fendiline producing a moderate increase in G0/G1 phase cells (49.2%), while higher concentrations resulted in pronounced G1 accumulation (73.2%) as compared to control cell fraction (43.2%). Conclusion: These findings demonstrate that fendiline exerts anti-proliferative effects in pancreatic cancer cells by disrupting cell cycle progression. Study supports further investigation of fendiline as a repurposed therapeutic cytostatic agent for pancreatic cancer and provides mechanistic insight into its anti-tumor activity.
Expression of cyclin dependent kinase 1 in colorectal cancer: A cell cycle regulator with prognostic potential
Background: Cell cycle regulation plays important role in maintaining cellular homeostasis. Dysregulation of the cell cycle is a hallmark of various diseases including cancer. In this study, the focus was to investigate expression profile of a major cell cycle related gene (CDK1) in colorectal cancer tissues and its active role in cell life. Methods: Tissue samples were collected from the patients diagnosed with colorectal cancer. Total RNA was extracted and gene expression levels were quantified via quantitative real-time PCR. Relative expression levels were estimated using ΔΔCt Livak method. Curated interaction pathway of CDK1 was generated using the NDEx Integrated Query platform to highlight the associated signaling networks. Results: CDK1 showed significant deregulation in the clinical samples compared to matched normal mucosa tissues. Overexpression of CDK1 was observed in the cases as compared to base level in control tissues. On average, a consistent induction was observed in stage I (2.6fold), stage II (4.7fold), stage III (3.5fold) and stage IV (3.99fold) cancerous tissues. Bioinformatic approach reflected the involvement of CDK1 in key cellular functions including G2 phase arrest, DNA replication, DNA repair, G1/S phase transition and mitotic activity, thereby indicating potential contribution to cancer progression and tumor development. Conclusion: The findings reflect clear induction of CDK1 gene in colorectal cancer tissues and may serve as a potential biomarker for prognosis. However, validation in larger cohort is needed to explore its utility in prognostic and therapeutic domains.
Artificial Intelligence in Oncology: Integrating Screening, Diagnosis, Prognosis and Treatment
Cancer is a global health challenge characterized by complex, adaptive biological processes and substantial mortality rates. Early detection and precise treatment personalization of cancer is elusive despite all the advances in oncological screening, diagnosis and treatment. Artificial intelligence (AI) emerges as a transformative technology in oncology by leveraging vast and varied datasets, including clinical records, genomic profiles, imaging, and pathology to augment decision-making and improve patient outcomes. AI encompasses machine learning (ML) and deep learning (DL) techniques capable of identifying intricate patterns in high-dimensional data unavailable to human cognition alone. These techniques are applied across the cancer care continuum, enabling improved risk stratification in screening, early diagnosis through radiological and histopathological image analysis, and enhanced prognostic modelling that surpasses traditional statistical methods. AI-driven models facilitate individualized treatment planning with adaptive radiotherapy, robotic surgery assistance, and optimization of chemotherapy and immunotherapy regimens, improving therapeutic efficacy while minimizing toxicity. This review synthesizes evidence across AI-driven screening, diagnosis, prognosis, treatment optimization and drug discovery, highlighting methodologies, clinical performance and future directions for AI in oncology. Key findings demonstrate that AI achieves expert-level performance in imaging-based cancer screening (mammography, colonoscopy, dermoscopy), surpasses traditional statistical models in multi-cancer prognostic prediction, and enables individualized treatment planning through adaptive radiotherapy, robotic surgical guidance, optimization of chemotherapy and immunotherapy regimes. Emerging applications in generative drug engineering and multi-cancer liquid biopsy detection further highlight AI’s expanding translational potential.
SLITRK6 in Cancer Metastasis: Emerging Evidence, Mechanisms and Therapeutic Potential
Cancer metastasis is a complicated biological process where cells from the primary tumour site spread into other organs far from the origin and cause a secondary tumour. The cascade of metastasis includes epithelial to mesenchymal transition (EMT), in which cancerous cells lose the epithelial characters and acquire features of migration and invasion through key signalling pathways as TGF-β, Wnt/β-catenin, and Notch. After EMT, cells can intravasate into the blood or lymphatic vessels, and extravasate into remote tissues, causing secondary tumours. Current cancer therapies are often ineffective against metastatic disease, and therefore, new approaches that target metastasis specifically are needed. SLIT and NTRK-like family member 6 (SLITRK6) promotes the migration of cancer cells by binding to ROBO receptors and controlling Rho GTPases, which are essential for cytoskeletal dynamics. Moreover, it also impacts the tumor microenvironment by regulating the interactions of immune cells and by promoting the secretion of MMPs, which facilitate tissue invasion. This review discusses the current understanding of SLITRK6's biological functions, especially in the context of cancer, and discusses the molecular pathways through which it influences metastasis. By targeting SLITRK6, it may be possible to disrupt both the migratory behavior of cancer cells and the supportive microenvironment that facilitates metastasis. Recent studies have identified SLITRK6 as a significant player in cancer metastasis. Its expression is associated with poor prognosis in several cancers. This review aims to provide a comprehensive overview of SLITRK6 in cancer metastasis and its potential as a novel therapeutic target.
Erufosine mediated regulation of apoptotic, cell cycle and cell survival genes in breast cancer cells
Background: Breast cancer is a common cancer in females worldwide with continuously growing incidence over the decades. Novel compounds are needed to treat breast cancer effectively. Erufosine, a synthetic lipid, is a promising anticancer agent that acts on cell membranes to induce antitumor effects and interfere with lipid homeostasis leading to toxic effects. Methods: Toxic effects of erufosine on human breast cancer cell lines were determined by MTT dye assay. Cell lines (MCF-7 and MDA-MB-231) were cultured and treated with erufosine for 24-72 h. Expressional changes in apoptosis (BCL2), cell cycle (CDKN1A) and cell survival (MYB) related genes were determined by real-time PCRs. Results: The compound induced cytotoxic effects in the cells in concentration dependent format. Both cancer cell lines were found sensitive towards the exposure with erufosine. Selected genes were de-regulated by the compound in cell specific format. Cell cycle inhibitor gene (CDKN1A) was up-regulated while cell survival (MYB) was down-regulated in the cells. Apoptosis (BCL2) gene showed a variable response in the two cell lines. Conclusion: Erufosine induces cell death in breast cancer cells and de-regulate the associated genes. Erufosine mediated observed functional and molecular changes in breast cancer cells highlight its antineoplastic potential.
Alkyl-phospholipids and cell cycle check point inhibitor induce antineoplastic effects in breast cancer cells: Evidence from in vitro investigations
Background: Combination of anticancer compounds often lead to better control of tumor progression. In this context, searching for novel combinations of anticancer compounds is a continuous process. Alkyl-phospholipids are synthetic lipids and have shown anticancer effects. Combining the alkyl-phospholipids with potential other drugs is an attractive filed of interest. In this study, we investigated the combined anticancer effects of an alkyl-phospholipids (erufosine and perifosine) and a cell cycle check point inhibitor (ATR) with the hypothesis that combining the two above-mentioned classes can be instrumental against breast cancer. Methods: Human breast cancer cell lines (MDA-MB-231 and MCF-7) were exposed to the two compounds and resulting toxicity was assessed by using a mitochondrial based dye reduction assay. The effects were calculated numerically, and percentages were compared with untreated controls. To give insights at gene levels, expression profiles of cell cycle associated genes (CDKN family) were investigated by using real-time PCR methos. The effects in both assays were uncovered as single agent and combinational approaches in parallel for comparison purposes. Results: Exposure with the compounds (erufosine, perifosine and AT inhibitor) reduced the cell proliferation of the breast cancer cells. Overall, alkyl-phospholipids induced more effectively the cell proliferation as shown by the MTT assay. Combination of the two classes (alkyl-phospholipids and ATR inhibitor) showed synergistic effects while inhibiting cell proliferation. The effects were comparable in the two breast cancer cell lines. The compounds either as single agent or in combination also induced the expression of CDKN family members. However, these effects were less pronounced in triple negative cells (MDA-MB-231) as compared to ER/PR positive cells (MCF-7). Conclusion: Alkyl-phospholipids and ATR inhibitor can be combined to achieve synergistic antineoplastic effects against breast cancer. Keywords: Breast Cancer, Alkyl-phospholipids, Cell cycle inhibitor, Combinational therapy
Expression profiling and bioinformatics of replication associated genes (MCM3 and MCM4) in colorectal cancer patients
Background: Mini-Chromosome Maintenance (MCM) genes encode proteins that are crucial for DNA replication in cells. These genes are often associated with the pathogenesis of cancer. Identification of their expression levels and physiological importance in cells is crucial for their potential utilization in cancer prognosis and treatment. Two members of the MCM gene family (MCM3 and MCM4) were targeted in this study, with a particular focus on colorectal cancer. Methods: Clinical tissue samples were obtained from colorectal cancer patients representing various disease stages. Expression profiling at the mRNA level was conducted using real-time PCR, and analysis was done via the Livak (2⁻ΔΔCt) method. STRING software was used to identify protein–protein interactions along with key biological processes and molecular functions associated with the two genes. Results: Distinct expression levels were observed for the two genes when healthy controls were compared with colorectal cancer patients. Overall, there was marked upregulation of the MCM3 gene in all four stages of colorectal cancer. Similarly, moderate upregulation of the MCM4 gene was observed in the patients. Bioinformatic analysis revealed important protein interactors for both genes, while key biological and molecular features such as DNA replication, helicase activity, double strand break repair, and regulation of replication were associated with them. Conclusion: The higher expression of MCM3 and MCM4, along with their crucial roles in cellular replication, makes them valuable targets for understanding colorectal cancer progression and potential therapeutic intervention.
Copyright (c) 2025 Copyright (c) 2025 Authors publishing manuscripts with Biology Circle journals agree to transfer copyright to the journal and will grant journal’s right to publication under CC-BY 4.0 license. Authors are strongly encouraged to distribute the published work at their personal levels including social media pages, academic websites and institutional repositories etc. https://creativecommons.org/licenses/by/4.0
Cell death induced by a non-selective calcium channel blocker (Fendiline) in colorectal and breast cancer cells
Background: Breast and colorectal cancer are two leading malignancies. Potential of available chemotherapies against these cancers need to be explored. Fendiline is a calcium channel blocker and has shown anticancer potential against cancers. By using the in vitro approach, we studied the toxic effects of fendiline against breast and colorectal cancer. Methods: Cancer cell lines for breast (MDA-MB-231 and MCF-7) and colorectal (SW480, SW620, Caco-2) were cultured and exposed to fendiline (0.75-100µM) for three-time intervals (24-72h). Resulting toxic effects were explored by using a dye reduction assay and were compared as percentages of untreated controls. Results: All the selected cancer cell lines showed comparable toxic profile of fendiline (IC50: 5.9-9.3µM, 72h). The cell lines demonstrated a steep decline in the growth curve at concentrations higher than 6.25µM. The toxic effects were concentration and time dependent in all five cell lines representing breast and colorectal cancer. Conclusion: Fendiline holds a very promising cytotoxicity profile against breast and colorectal cancer. Provided with further studies, the drug can be used against the two malignancies in clinical scenarios.
Ribosomal inactivating plant protein: The regulator of tumor suppressor and oncogenes in breast cancer
Background: Breast cancer, a leading malignancy in females, accounts for a significant proportion of cancer related deaths worldwide (~12%). Novel medicines are required to control disease burden. Plants genera is a big source for naturally occurring anticancer compounds. Riproximin, a purified protein obtained from a plant, has shown substantial anticancer potential against cancer cells. The current study was designed to identify cytotoxic effects and expressional changes in tumor suppressors and oncogenes at transcriptome levels induced by the selected ribosomal inactivating plant protein (riproximin) in breast cancer cells. Methods: In preliminary phase, toxic effects of the protein were identified against breast cancer cells (MDA-MB-231) by a dye reduction assay. In a separate experiment, the cells were exposed to the protein and expressional modulations in 3 selective tumor suppressors and oncogenes (REL, FOS, KITLG) were identified by using a ready-made PCR methodology. Results: Riproximin induced anti-proliferative effects in the breast cancer cells. Exposure of the cells with various concentrations of riproximin showed concentration dependent effects of the compound on expressional profile of the selected genes. The three genes were substantially induced in the cells. Conclusion: Riproximin bears significant cytotoxic potential and modulates the genes in breast cancer cells.
Riproximin mediated cytotoxicity and expression modifications in lung cancer cells
Background: Worldwide, lung cancer is the leading malignancy and responsible for ~20% of cancer related deaths. Evidence from clinical data shows an objective response from currently available therapeutic approaches, especially against advance stages of lung cancer, which in turn, highlight the need to identify novel treatment modalities with better efficacy and lesser off target effects. A ~60kDa active protein component was purified from of the plant Ximenia american. The purified protein (riproximin) has shown cytotoxic effects over the years against cancer cells and in the animal models. Methods: Effects of riproximin on cell viability were investigated by MTT dye reduction methodology. Briefly, the lung cancer cell line (H1299) was cultured in 96-well plate and treated with different concentrations of riproximin (0.39- 25ng/ml) for three different time points (24, 48 and 72 hours). After each time interval, MTT solution was added, and concentration of viable cells were determined by ELISA plate reader. Later, the impact of riproximin on selective genes were analyzed by real time PCR strategy. The data was compared with the expression profile of untreated control cells, and fold changes were calculated via Livak method. Results: The cytotoxic effects of riproximin were time and concentration dependent as more prominent toxicity was observed with increasing concentrations especially for late time intervals (48 and 72 hours). At highest concentration (25ng/ml), the maximum growth inhibition was observed (85%) after 72 hours. Substantial riproximin mediated expressional modulations in related genes were shown by real time PCR. Specifically, CCND1 and CASP3 genes were inhibited, while SERTAD1 and GADD45A were induced in response to riproximin exposure. Conclusion: Riproximin is a substantial cytotoxic compound and induces prominent anti- proliferative effects in lung cancer cells. Furthermore, the compound has potential to alter the expressional profile of genes. The current study provides vital data about antineoplastic effects of riproximin against lung cancer cells and will provide a platform for further studies and clinical utilization of this protein to treat lung cancer overtime.
Copyright (c) 2024 Copyright (c) 2024 Authors publishing manuscripts with Biology Circle journals agree to transfer copyright to the journal and will grant journal’s right to publication under CC-BY 4.0 license. Authors are strongly encouraged to distribute the published work at their personal levels including social media pages, academic websites and institutional repositories etc. https://creativecommons.org/licenses/by/4.0
CXCL family of chemokine: Clinical perspective in colorectal cancer
Background: Chemokine are small proteins which play a critical role in colorectal pathophysiology by stimulating inflammation, influencing angiogenesis and movement of immune cells. Recent research has emphasized the possible role of CXC chemokine family in influencing cancer development. In this study, focus was to investigate the CXC chemokines as potential biomarkers in colorectal cancer by comparing their levels in primary phases. Methods: This comparative cross-sectional study was conducted while using serum samples of colorectal cancer patients (stage II & III) and healthy controls. The circulatory levels of CXCL chemokines were quantified by using enzyme-linked immunosorbent assay (ELISA) and differences between chemokine levels of colorectal cancer patients and healthy controls were analyzed using an independent t-test via the latest version of SPSS. Results: The study findings showed that concentrations of CXCL1, CXCL9, and CXCL11 chemokine were raised considerably with colorectal cancer progression, particularly in stage III, indicating their involvement in cancer progression. CXCL10 and CXCL11 concentrations were found to be significantly altered between the two stages of colorectal cancer (p<0.05). Conclusion: CXCL levels de-regulate in colorectal cancer and may serve as biomarkers and therapeutic targets.
PDL1 and KRAS: Immune system evasion and genetic aberrations in cancers
Cancer is a leading global health concern, representing a significant burden on healthcare systems due to its high morbidity and mortality rates. The World Health Organization reports that cancer is the second leading cause of death worldwide, with millions of deaths attributed to this disease annually. The rising incidence of cancer cases necessitates ongoing research and the development of innovative treatment strategies to improve patient outcomes. Among the promising advancements in cancer therapy is immunotherapy, which aims to enhance the ability of immune system to recognize and combat cancer cells. Immune checkpoint inhibitors, such as those targeting the PD-1/PD-L1 pathway, have gained attention for their potential to reactivate T cells and bolster anti-tumor responses. This review focuses on the mechanisms regulating PD-L1 expression and the role of KRAS mutations in tumor progression and immune evasion. PD-L1, a protein that interacts with PD-1 on T cells, plays a crucial role in dampening immune responses, allowing tumors to evade detection and destruction by the immune system. The review discusses various factors influencing PD-L1 expression, including transcriptional regulation by key signaling pathways and the impact of inflammatory cytokines within the tumor microenvironment. Additionally, it highlights how genetic alterations, particularly KRAS mutations, can drive PD-L1 overexpression and contribute to tumor aggressiveness. In conclusion, understanding the complex interplay between PD-L1 expression and KRAS mutations is essential for developing targeted immunotherapies and enhancing precision medicine approaches in oncology. By elucidating these mechanisms, researchers can identify new therapeutic targets and improve treatment strategies, ultimately aiming to enhance patient survival rates and quality of life in cancer care. This review underscores the importance of ongoing research in this area to address the challenges posed by cancer's heterogeneity and resistance to existing therapies.
Ribosome inactivating plant protein mediated regulation of transcriptomic profile in liver cancer cells
Background: Hepatocellular carcinoma (HCC) is the primary malignancy of the liver that accounts for about 90% of liver cancers. Utilization of natural compounds could be instrumental for HCC patients with better therapeutic efficacy and lesser side effects. A plant based ribosomal inactivating protein (riproximin) has shown substantial antineoplastic properties against the variety of cancer cell lines. The purpose of this study was to investigate the cytotoxic effects of riproximin on cell proliferation of liver cancer cells and to determine the expressional changes induced in cell cycle and cell stress relevant genes. Methods: The HepG2 cell line (liver cancer cells) was cultured in under suitable conditions and exposed to different concentrations of riproximin (0.38–50ng/ml) for 24-72 hours followed by cytotoxicity analysis. Afterwards, the cells were exposed to riproximin (1-20ng/ml) for 48 hours and RNA was extracted using a commercial extraction kit. RT PCRs were carried for analysis of cell cycle (CCND1, CDKN1A) and cell stress (GADD45A) relevant genes. Fold changes were calculated by Livak 2-ΔΔCT method by comparing Cq values of experimental (riproximin treated) and untreated control samples. Results: Findings revealed concentration and time dependent inhibitory effects of riproximin on liver cancer cells. The growth inhibition was maximum at 72 hours with 50ng/ml concentration. RT PCRs results showed that riproximin inhibited the expression of cell cycle promoter gene (CCND1), while cell cycle inhibitor (CDKN1A) and cell cycle inducers (GADD45A) were up regulated. Conclusion: Riproximin harbors significant cytotoxic effects against liver cancer cells. Expressional variations in multiple related genes are imposed by riproximin in the liver cancer cells.
Alkyl-phospholipid mediated cytotoxic and cytostatic effects in liver cancer cells
Background: Hepatocellular carcinoma is a prevalent cancer in the world. Due to limited therapeutic options, this malignancy is causing substantial morbidity and mortality world-wide. Alkyl-phospholipids (ALPs) are synthetic lipids and comprise a promising class of anticancer compounds. Erufosine is the latest available generation of this class and has shown anti-tumor effects against a variety of cancer cell lines. This study was designed to uncover its cytotoxic and gene expression modulations by erufosine in liver cancer cells. Methods: Human liver cancer secondary cell line (HepG2) was cultured and exposed to erufosine. Afterwards, cytotoxic effects were monitored via MTT assay. Following the exposure with the compound, gene expression analysis of cell cycle related genes (CCNA1, CCNA2, and CCND1) was performed by using real-time PCR methodology. Results: Erufosine demonstrated substantial cytotoxicity in liver cancer cells with increased cell death at higher concentrations and longer exposure intervals. Erufosine imposed discrete expression modifications in the selected genes, where CCNA1 and CCND1 genes were up-regulated while CCNA2 was down-regulated in response to the treatment. Conclusion: Erufosine is a significant anticancer compound and needs further attention to translate it as a medicine.
Platelet Factor 4: A targetable chemokine induces antineoplastic effects in colorectal cancer cells
Background: Platelet Factor 4 plays an important role in tumor cell proliferation, migration and invasion. Platelet Factor 4 is an angio-static chemokine that acts as an immunosuppressant in tumor microenvironment by inhibiting T cell mediated anti-tumor immune response. Due to chemoattractant properties, it appears to be an important marker in cancer progression. In this study, Platelet Factor 4 was inhibited in the colorectal cancer cells followed by concomitant effects on functional properties of the colorectal cancer cells. Methods: Platelet Factor 4 gene was knocked down by siRNA in human (Caco2) and rat (CC531) colorectal cancer cells. MTT assay was used to observe colorectal cancer cell survival following the Platelet Factor 4 knockdown, while trans-well migration assay, scratch assay and colony forming assays were used to investigate the ability of colorectal cancer cells to migrate and form colonies respectively. Results: Knockdown of Platelet Factor 4 causes decrease in proliferation of the colorectal cancer cells. Inhibition of the gene also reduced the migration, colony formation and wound healing properties of colorectal cancer cells. The effects were visible and comparable in the human and rat colorectal cancer cell lines. Conclusion: Down-regulation of Platelet Factor 4 gene may serve as a therapeutic target in colorectal cancer.
Cytotoxic effects and expressional modifications induced by alkyl-phospholipid (erufosine) in lung cancer cells
Background Lung cancer is the leading cause of morbidity and mortality in the world. Treatment of lung cancer is a challenge because of the aggressive nature of this disease and limited therapeutic options. The situation demands to investigate novel compounds for better treatment of lung cancer with lesser side effects. Alkyl-phospholipids (ALPs) are an attractive class of antineoplastic agents which target DNA and act upon cell membranes to produce anticancer effects in tumour cell specific manners. Erufosine is the 3rd generation ALP and induces anticancer effects by causing changes in the lipid rafts of the cell membrane. Methods: Selected lung cancer cell line (H1299) was cultured in 96-well plates and exposed to various concentrations of Erufosine (1.56-50µM) followed by MTT dye-based assessment of viable cell fractions. For expression modifications, the cells were exposed to Erufosine followed by RNA extraction, cDNA synthesis and real-time PCR based assessment of the selected genes modulations. Results: Erufosine induced substantial cytotoxic effects in the lung cancer cells as shown by growth inhibition of 25 and 50% by using 24 and 33µM concentration respectively. At lower concentrations (6.25µM), there were negligible cytotoxic effects, which gradually increased with increasing concentrations. As far as expressional changes are concerned, the three selected genes (CCNB1, CDKN3, CASP3) were down-regulated in response to Erufosine exposure. Conclusion Erufosine is a potential cytotoxic compound, induces notable anti-proliferative effects and modulate expressional levels of the genes in lung cancer cells.
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Cytotoxic effects of synthetic alkyl-phospholipid (Erufosine) in combination with chemotherapy (5-FU) against colorectal cancer cells
Background: Colorectal cancer (CRC) is one of the most commonly diagnosed malignancy. An approach used in treatment of this cancer is combinational treatment where anticancer compounds are combined for cure. Exploring the novel anticancer compounds for potential usage as combinational approach is burning domain. In this regard, alkyl-phospholipids are novel agents and erufosine is a 3rd generation alkyl-phospholipid compound that interact with surface membrane of cell and induces antineoplastic effects in malignant cells. Material and Methods: Toxic effects of erufosine and 5-FU (5-FU) were identified against the CRC cell lines. For this purpose, the cells were exposed to various concentrations of the test compounds for 24-72 h and cell viability was assessed by MTT dye reduction assay. Afterwards, the cells were exposed to three distinct concentrations of the test compounds (IC25, IC50, IC75) for 48 h and expressional modulations in cell cycle regulator (P21) and stress marker (GADD45A) were identified by qRT-PCR methodology. For both MTT assay and qRT-PCR analysis, the cells were exposed to selected compounds as single agent or combination in parallel to avoid any time-lapse related differences between the experimental findings. Results: Erufosine and 5-FU induced substantial anti-proliferative effects in SW480, SW620, HCT116 CRC cells. The inhibitory effects of erufosine were more pronounced in comparison to 5-FU. Furthermore, synergistic anti-proliferative effects were observed when erufosine was combined with 5-FU. In addition, qRT-PCR data showed noteworthy potential of the test compounds to induce expression of P21 and GADD45A genes at mRNA levels in the cells. Precisely, combination of erufosine and 5-FU induced P21 gene more prominently in the cells, especially in metastatic CRC cells (SW620). Conclusion: Erufosine and 5-FU bear substantial cytotoxic potential against the CRC cells. Combination of erufosine and 5-FU showed synergistic anti-proliferative effects in the cells. The compounds up-regulate expression of a cell cycle inhibitor and cell stress marker (P21 and GADD45A gene) in CRC cells.
Effects of chemokine receptor 5 (CCR5) blockage on cell survival and expression levels of apoptosis related genes (FAS, FASL) in hepatocellular carcinoma cells
Background: Hepatocellular carcinoma (HCC) is a malignant tumor which arises from the liver cells (hepatocytes). HCC is 3rd leading cause of cancer related mortalities worldwide. Various treatment strategies for HCC include surgery, radiotherapy, targeted agents and chemotherapy. Despite the availability of diverse therapeutic options, 5-year survival rates are low (10-30%) especially in advanced stages of HCC. This, in turn, highlights the need to identify new therapeutic targets/compounds for HCC treatment. Purpose of this study was to evaluate effects of blocking a chemokine receptor (CCR5) on cell proliferation and apoptosis related genes (FAS/FASL) in HCC cells (HepG2). Materials & Methods: CCR5 receptor was blocked by using an FDA approved antagonist (Maraviroc) in HepG2 cells and effects on proliferation were identified. For this purpose, the cells were exposed to various concentrations (7.5-500µM) of the test compound and cell viability was monitored by MTT dye reduction assay for 24, 48 and 72 hours. Afterwards, HepG2 cells were exposed to three distinct concentrations of maraviroc (IC25, IC50, IC75) in a separate experiment and expressional modulations in two apoptosis related genes (FAS and FASL) were identified by qRT-PCR methodology. Results: The results indicated that blocking CCR5 via maraviroc induced substantial anti-proliferative effects in HepG2 cells. The effects were time and concentration dependent and were especially clearer following exposure with 100µM of maraviroc. Blockage of CCR5 induced marginal up-regulation of FAS gene in the cells. In contrast, blocking of CCR5 inhibited the expression of FASL gene in HepG2 cells in a concentration dependent format with a maximum inhibition of 5fold. Conclusion: CCR5 blockage by maraviroc induces prominent cytotoxic effects in HCC cancer cells. Expressional modulations in apoptosis related genes are imposed in response to blockage of the chemokine receptor in the cells. Further studies are needed to understand the precise nature of growth inhibitory effects observed in response to blockage of CCR5 in HepG2 cells.
Riproximin mediated effects on transcriptomic profile of PI3K-AKT-mTOR pathway genes in breast cancer cell lines
Background: Riproximin, a type II ribosome inactivating protein, is a substantial antineoplastic agent and can be used as alternative to chemotherapy specifically to kill tumour cells. Since discovery, this protein has been tested against various cancer cell lines and animal models to explore its anti-neoplastic activities. In this study, riproximin has been tested to unfold its impact on multiple genes related to PI3K/Akt/mTOR signaling pathway. This pathway has its significant importance in regulation of cellular functions which include metabolism, proliferation, survival and growth of cancerous cells. For it valuable importance during carcinogenesis, this pathway is also being targeted for therapeutic purpose. Materials and Methods: MTT dye reduction assay was used to find out toxicity of riproximin by exposing the selected breast cancer cell lines (MDA-MB-231 and MCF-7) with different concentrations (1-50ng/ml) of the protein. Afterwards, in a separate experiment, the cell lines were exposed to different concentrations (MDA-MB-231: 1-50ng/ml, MCF-7: 1-20ng/ml) of riproximin followed by total RNA extraction, cDNA synthesis and expressional profiling of 10 genes related to PI3K-AKT-mTOR signaling by using real-time PCR. Fold changes were identified via Livak method while comparing the data with untreated cells grown in parallel. Results: MTT assay results showed that riproximin induced significant toxic effects in the breast cancer cell lines, where MDA-MB-231 cells were less sensitive (IC50: 10.2ng/ml) as compared to MCF-7 (IC50: 1.8ng/ml) cells. Real-time PCR demonstrated a substantial potential of riproximin to alter the expression of cell cycle associated genes. Among these targets, most effective de-regulations in MDA-MB-231 cells were found in FOS (16fold) followed by JUN (6fold) and NFKB1 (4fold). In MCF-7 cells, most substantial modifications were observed in NFKB1 (14fold), CD14 (9fold) and PDK1 (6fold). Conclusion: Riproximin bears significant cytotoxic potential against primary and metastatic breast cancer cell lines. Substantial expressional modulations in PI3K/Akt/mTOR signaling pathway related genes are imposed by riproximin in the cancer cells. Further detailed in vitro and in vivo studies are required to understand the precise impact of riproximin exposure on PI3K-AKT-mTOR signaling, which ultimately will pave the way for its clinical utilization.
Nanoparticles and drug delivery for chemoprevention in cancers
Cancer is a major global issue that is responsible for morbidity and mortality all over the world. Radiation therapy, surgery, and chemotherapy are categorized into traditional cancer treatment methods that cause systemic toxicity and limited efficacy due to the effect of non-specific drug delivery. As a result, various side effects compromise a patient’s quality of life. So, for the treatment of cancer, many innovative approaches are required that can enhance therapeutic outcomes and result in fewer adverse effects. Nanotechnology addresses such challenges and provides a promising avenue for treating cancer. Engineered nanoparticles offer a platform for targeted drug delivery, that enhances therapeutic efficacy and shows minimum adverse effects. In this way, researchers have now developed strategies to improve cancer chemoprevention. This review demonstrates the application of various nanoparticles in cancer chemoprevention and focuses on their mechanisms of action, advantages, and novel research advancements. In cancer chemoprevention, the mechanisms of action of nanoparticles are diverse and are dependent on targeted cancer and particular nanoparticle types. Nanoparticles can inhibit tumor cell proliferation, induce apoptosis, and cause tumor cell differentiation. They can promote an immune response against tumor cells causing the effective anti-tumor effect. Researchers are developing various novel nanoparticle platforms having improved targeting efficiency, biocompatibility, and drug release kinetics. Furthermore, researchers are also trying to combine nanoparticles with other therapeutic applications such as immunotherapy, to get synergistic anti-tumor effects.
Anticancer effects of a silkworm protein (sericin) in lung cancer cells
Background: Lung cancer is a wide-spread malignancy across the world. With the limited availability of therapeutic options, 5-year survival is low in advanced stages of lung cancer. Sericin, a biowaste protein from silkworm cocoon has shown anti-cancer potential against various cancers in pre-clinical research with minimal side-effects. Current study was designed to determine cytotoxic effects and expression modulations imposed by sericin in lung cancer cells. Materials & Methods: Sericin from local cocoons was extracted via degumming process. Human lung cancer cells (H1299) were cultured and exposed to different concentrations of extracted and commercially available sericin (0.03-1 mg/ml) for 24-72 hours. Effects on proliferation were determined by MTT dye reduction assay. Following the total RNA extraction and cDNA synthesis, expressional alterations in cell cycle (CDKN1A, CDKN1B) and stress (GADD45A, GADD45B) relevant genes were determined via real-time PCR methodology. Results: Sericin exposure induced the concentration and time dependent inhibitory effects on cancer cell proliferation. Comparable results from commercially available sericin and local extracted sericin confirmed the reliable extraction process adopted in this study. CDKN family of genes (cell cycle inhibitors) was up-regulated in response to the sericin exposure. GADD genes (markers of cell stress) were also induced in the cancer cells in response to sericin exposure. Conclusion: Lung cancer cells were responsive towards sericin exposure as observed by inhibition of the proliferation. Sericin interfered with expression levels of cell cycle inhibitor and stress related gene families. Further studies are needed to understand the anticancer potential of sericin against lung cancer cells.