Methotrexate Combination Effects with Genistein and Daidzein on MDA-MB-231 Breast Cancer Cell Viability

Ashleigh Maginnes, Richard Owusu-Apenten
2017 Journal of Applied Life Sciences International  
Aims: To investigate the effect of methotrexate and soy isoflavones genistein and daidzein on MDA-MB-231 breast cancer cell viability. Methods: Human breast cancer MDA-MB-231 cells were cultured in DMEM (with 10% FBS, 1% Pen strep) and treated with methotrexate, genistein or daidzein for 72 hrs. Combinations treatments used non-fixed ratios of methotrexate (0-100 µM) and genistein or daidzein (30 µM) with cell viability monitored using the MTT assay. Results: The 50% effect dose (EC50) was
more » ... ose (EC50) was 44.7±6.4 µM for methotrexate, 55.8±3.9 µM for genistein or 67.4±12.2 µM for daidzein. Combination treatments with genistein or daidzein Maginnes and Owusu-Apenten; JALSI, 13(1): xxx-xxx, 2017; Article no.JALSI.35206 2 produced EC50 of 57.6±2.0 or 29.7±2.4 µM for methotrexate, respectively. The combination index (CI) was 1.9 for methotrexate-genistein whilst CI was 1.1 for methotrexate-daidzein near the median dose. Values for CI decreased from 5.0 towards 1.0 as the ratio of methotrexate: isoflavone increased. The results are discussed in terms of prevailing ideas concerning how phytochemicals affects drug adsorption, distribution, metabolism and excretion (ADME) and the expected consequences for cytotoxicity. Conclusions: Treatment of MDA-MB-231 breast cancer cells with methotrexate and genistein or daidzein produces interactions consistent with antagonism (CI =1.1-5.0) but the effects are predicted to diminish with rising methotrexate to isoflavone ratio. Short Research Article
doi:10.9734/jalsi/2017/35206 fatcat:hgrscpbx4fbdzfhbnjbys45vyu