Sequential Therapy of Breast Cancer Cell Lines with Vitamin C and Quercetin Improves the Efficacy of Chemotherapeutic Drugs

ABSTRACT

Objective: Prevention by antioxidant agents including vitamin C (VC) and quercetin (QU), which are nontoxic, cost effective, and physiologically bioavailable, is a promising approach in breast cancer handling. The aim of this work is to investigate the influence of VC+QU on cytotoxicity profile of doxorubicin (DOX) plus paclitaxel (PAC) in breast cancer cells. Methods: The effect of each drug on its own or in combination was evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Combination indexes were calculated using the Chou–Talalay method. Apoptosis and cell cycle analysis was investigated by flow cytometric assays. Results: Combination treatment with VC+QU plus drugs diminished IC₅₀ value 2.28–7.7 and 10.5–66.6 fold in comparison with the drugs and PAC treatment alone, respectively, in all breast cancer cells and induced apoptosis at the early stages more than the treatment with the drugs alone (P<0.01). A marked reduction in Go/G1 and S phases was reported after combination therapy in MDA-MB 231 and MDA-MB 468 cells. MCF-7 cells demonstrated lower fractions of cells in S phase with no significant changes in G2/M phase (P < 0.01). The same treatment produced a significant increase in S and G2/M phases in A549 cells (P < 0.001). Conclusion: Our results emphasized the importance of VC+QU in combination with the drugs to produce a synergistic antitumor effect in breast cancer cells.

Acknowledgments

This study was performed as a part of PhD student thesis by Fatemeh Ramezani, who is supported by grant no. 92–6659 from the office of Vice Chancellor for Research and the Committee for Advanced Biomedical Sciences, Shiraz University of Medical Sciences, Shiraz, Iran. The authors would like to thank the Student Research Committee of Shiraz University of Medical Sciences. The authors would also like to thank Dr. Zomorodian, Mr. Hossaini, Ms. Rezaei, and Ms. Shobeyri, Institute of Cancer Research, Shiraz University of Medical Sciences, for real-time PCR, apoptosis, and cell cycle assays assistance.