Ataxia-Telangiectasia Mutated (ATM) inhibitor induces antineoplastic effects in brain cancer cells: Evidence from in vitro investigations
DOI:
https://doi.org/10.63626/21zenk44Keywords:
Brain cancer, Ataxia-Telangiectasia Mutated, Anticancer effects, Apoptosis, Cell cycleAbstract
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.
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