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Y15 Enhances the Cytotoxic Profile of Cisplatin, Paclitaxel and Vitamin E in Platinum Resistant Ovarian Cancer Cells
Author(s) -
Reboe Monique,
Levy Arkene,
Dhandyuthapani Sivanesan,
Rathinavelu Appu
Publication year - 2015
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.29.1_supplement.785.1
Subject(s) - paclitaxel , cisplatin , ovarian cancer , cytotoxic t cell , cytotoxicity , platinum , cancer research , vitamin e , medicine , pharmacology , oncology , cancer , chemistry , chemotherapy , in vitro , antioxidant , biochemistry , catalysis
Objectives: Ovarian cancer treatment with cisplatin and paclitaxel is often complicated by a high rate of recurrence due to development of resistance which has been linked to overexpression of the tyrosine kinase Focal Adhesion Kinase (FAK). Recently, vitamin E succinate (VES) has demonstrated significant cytotoxic efficacy in a variety of cancers. Thus, this study assessed the combined effects of FAK inhibitor Y15 with vitamin E, Cisplatin and Paclitaxel in overcoming resistance in a platinum resistant ovarian cancer cell line. Method: OVCAR‐3 cells were treated with varying concentrations of Y15, combinations of Y15 or VES with cisplatin + paclitaxel for 24 hrs in triplicate and control cells with DMSO or media only. The cytotoxic profile of each treatment was assessed using the automated trypan blue assay and DNA fragmentation assay was performed to evaluate the mechanism of cell death. Results: Dose dependent and statistically significant cytotoxicities were seen with Y15 and VES compared to controls with IC 50 values 80 µM and 258 µM respectively. For combination treatments, Y15 significantly increased percentage cell death when combined with cisplatin+ paclitaxel (27.15 %) and VES (20.33%). Cell death by apoptosis was confirmed by DNA fragmentation in Y15 and VES treated groups. Conclusion Y15 significantly enhances the cytotoxic profile of cisplatin, paclitaxel and VES in resistant OVCAR‐3 cells, suggesting that targeting FAK activity through the inhibition of Y397 site, augments resistance to paclitaxel, cisplatin and VES. Funding: UWI, Office of Graduate Studies & Research