Doxorubicin Cytotoxicity in Combination with Soy Isoflavone Daidzein on MCF-7 Breast Cancer Cells

ABSTRACT

Introduction: Combination chemotherapy regimens offer a promising approach to the prevention of recurrence, metastasis and drug resistance during breast cancer management. Combined tumor therapy using natural substances is highly suggested. Daidzein is one of the major isoflavones in soy beans with anti-tumor activity but its effect in combination with common chemotherapeutic agents is still unclear. This study was designed to investigate whether daidzein increases the antitumor activity of doxorubicin against MCF-7 human breast cancer cells. Methods: The cytotoxic activity of doxorubicin, daidzein and a combination of the two drugs was determined at different concentrations using LDH release assay. The average values of each experiment were adjusted to the values determined from untreated controls and 50% inhibitory concentration (IC.) value for each drug was calculated by CompuSyn. In vitro interaction was also calculated using different combinations of doxorubicin and daidzein. Combination indices (CI) were calculated and combination index plot was constructed using the same software. Results: Analysis of the dose-effect curve showed that the treatment of MCF-7 cells with doxorubicin or daidzein for 24 h led to 50% cytotoxicity at 5.4 nM and 146.5 respectively. Conclusion: The Combination index plot showed CI >1 for all combinations used in this study which indicates antagonistic interactions between daidzein and doxorubicin. This study results have implications for patients with breast cancer under treatment with doxorubicin if they are taking daidzein as a dietary supplement.