Objectives: The high drug-resistance associated with cisplatin and paclitaxel has complicated the treatment of ovarian cancer. This resistance has been linked to over-expression of focal adhesion kinase (FAK). More recently, a therapeutic platform for vitamin E was established in cancers and therefore, the present study assessed the cytotoxic effects of the FAK inhibitor 1, 2, 4, 5-Benzenetetraamine tetrahydrochloride (Y15) or vitamin E (alpha tocopherol succinate/VES) in combination with cisplatin and paclitaxel in a platinum resistant ovarian cancer cell line.
Method: Platinum-resistant OVCAR-3 cells were treated with varying concentrations of Y15 or vitamin E in combination with cisplatin plus paclitaxel over a 24 hours period in triplicate. Control cells were treated with media only. The cytotoxic profile of each treatment was determined using the automated trypan blue assay and DNA fragmentation assay was performed to evaluate the mechanism of induced cell death.
Results: Dose dependent and statistically significant cytotoxic effects were seen with Y15 and vitamin E only when compared to controls with IC 50 values of 80 µM (p < 0.015) and 250 µM (p < 0.02), respectively. Both Y15 and vitamin E (24% and 27.16 %) significantly increased the percentage cell death induced by cisplatin plus paclitaxel when given in combination. Cell death by apoptosis was confirmed from observed fragmented DNA in all Y15 and Vitamin E treatment groups.
Conclusion: Vitamin E and Y15 significantly enhanced the cytotoxic activity of cisplatin and paclitaxel in OVCAR-3 cells.