The natural isoflavone Biochanin‐A synergizes 5‐fluorouracil anticancer activity in vitro and in vivo in Ehrlich solid‐phase carcinoma model. (2nd February 2022)

• Record Type: Journal Article
• Authors: Mahmoud, Mohamed; Abdollah, Maha R. A.; Elsesy, Mohamed E.; Abou El Ella, Dalal A.; Zada, Suher K.; Tolba, Mai F.
• Is Part Of: Phytotherapy research. Volume 36:Number 3(2022)
• Page Start: 1310
• Page End: 1325
• Publication Date: 2022-02-02
• Subjects: 5‐fluorouracil -- apoptosis -- Biochanin‐A -- breast cancer -- synergism; Materia medica, Vegetable -- Periodicals; Botany, Medical -- Periodicals; Medicinal plants -- Periodicals; Plant Extracts -- therapeutic use -- Periodicals; Plants, Medicinal -- Periodicals; 581.634
• DOI: 10.1002/ptr.7388
• Languages: English
• ISSNs: 0951-418X

Abstract

Abstract: Isoflavones are considered one of the most extensively studied plant‐derived phytoestrogenic compounds. Of these, Biochanin A (Bio‐A), a natural isoflavone abundant in cabbage, alfalfa, and red clover, has drawn a lot of attention. As reported in multiple studies, Bio‐A possesses a promising anticancer activity against estrogen receptor–positive (ER+) breast cancer. The current study investigated the working hypothesis that Bio‐A could synergistically enhance the potency of 5‐fluorouracil (5‐FU) in ER+ breast cancer. The hypothesis was tested both in vitro on hormone receptor–positive (MCF‐7) and triple‐negative breast cancer cells (MDA‐MB231). Additionally, in vivo studies were performed in the Ehrlich solid‐phase carcinoma mouse model. The in vitro cytotoxicity studies revealed that Bio‐A synergistically increased the potency of 5‐FU in both MCF‐7 and MDA‐MB231 cell lines. The synergistic effect of 5‐FU/Bio‐A combination was verified in vivo. The combination therapy (where 5‐FU was used at one fourth its full dose) led to a significant 75% reduction in tumor volume after two treatment cycles. This was in addition to producing a significant 2.1‐fold increase in tumor necrosis area% compared to mock‐treated control. In conclusion, the current study presents the first preclinical evidence for the potential merit of 5‐FU/Bio‐A combination for the treatment of ER+ breast cancer. The synergistic antitumor effect of Bio‐A/ 5‐FU combination can be, at least partly, attributed to Bio‐A‐mediated suppression of ER‐α/Akt axis and the augmentation of 5‐FU‐mediated proapoptotic effects. © 2022 John Wiley & Sons, Ltd.