Antineoplastic effects of erufosine in combination with oxaliplatin in colorectal cancer

Abstract

Background: Combinations of the anticancer agents is a commonly practiced strategy in cancer treatment as it provides an efficient way to control the disease burden with reduced side effects. Finding novel compounds to be combined with the available chemotherapeutic drugs for better treatment of colorectal cancer is a much-needed research domain. In this context, alkyl-phospholipids comprise an attractive class of compounds which induce anticancer effects by targeting the cell surface membranes. Erufosine is a 3^rd generation of alkyl-phospholipid class and interacts with the surface lipid molecules of the cell membranes to induce antineoplastic effects in cancer cells.

Methods: Toxic effects of the selected alkyl-phospholipid (erufosine) and a commonly used chemotherapeutic agent (oxaliplatin) for colorectal cancer were identified in the three human cancer cell lines. For this purpose, the cells were exposed to various concentrations of the test compounds (single agent and combination) for 24-72 hours and cell viability was assessed. Afterwards, the cells were exposed to the distinct concentrations of the test compounds for 48 hours and expressional modulations in a cell cycle master regulator (P21) and stress marker (GADD45A) were identified by qRT-PCR methodology.

Results: The results indicated that erufosine and oxaliplatin induced substantial anti-proliferative effects in colorectal cancer cells. The inhibitory effects of erufosine and oxaliplatin alone were significantly pronounced. In addition, synergistic anti-proliferative effects were observed when erufosine was combined with oxaliplatin. In addition, qRT-PCR data showed noteworthy potential of the test compounds to induce expression of P21 and GADD45-A genes at mRNA levels in the cells. Combination of erufosine and oxaliplatin induced P21 gene more prominently in the cells, especially in metastatic colorectal cancer cells.

Conclusion: Erufosine and oxaliplatin impose substantial cytotoxic effects in the colorectal cancer cells. The combination of erufosine and oxaliplatin showed synergistic anti-proliferative effects. The compounds up regulated the expression of cell cycle inhibitor and cell stress marker (P21 and GADD45A) in colorectal cancer cells.