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