Antiproliferative effect of Saraca asoca methanol bark extract on triple negative breast cancer (TNBC)

Background Saraca asoca (Asoka) is reported to possess phytoestrogenic components with anticancer properties. The phytoestrogens are recognized as natural agonists for ER beta, which acts as an antagonist to ER alpha. Despite the absence of ER alpha, studies have identified ER beta in 50-80% of triple negative breast cancers (TNBC). Thus, the present study is intended to reveal the role of phytoestrogens of Asoka on TNBC. The cytotoxic effect of Asoka methanol bark extract was analyzed on different breast cancer cell lines by MTT assay. Estrogen-screen assay was employed to determine the proliferative/antiproliferative effect. Identification of phytoestrogens in Asoka was accomplished using LC-MS analysis and in silico docking studies were performed to investigate possible interactions of phytoestrogens with ER alpha and beta. Results The extract of Asoka was found to be cytotoxic against TNBC cell line, MDAMB-231 with IC50 of 70.22 +/- 1.89 mu g/mL and towards HER+ breast cancer cell line, SKBR3 with IC50 of 98.41 +/- 2.31 mu g/mL, respectively. Whereas the extract did not show any cytotoxicity towards ER alpha cell line, MCF-7 even up to the concentration 300 mu g/mL. Estrogen-screen assay emphasized an estrogenic effect of the extract on MCF-7 and an anti-estrogenic/antiproliferative effect on MDAMB-231 cells. LC-MS analysis identified phytoestrogens such as beta-sitosterol, quercetin, kaempferol and others. The docking results revealed good binding efficacy of phytoestrogens with ER beta than ER alpha and quercetin shows more affinity with the highest docking score of - 9.220. Strikingly, it was found that the S. asoca methanol extract was preferentially cytotoxic to TNBC cells. Conclusion The study demonstrates selective anticancer properties of S. asoca methanol extract on TNBC, which indicates a selective impact on ER subtypes. The identification of phytoestrogens, such as beta-sitosterol, quercetin and kaempferol, in the Asoka methanol bark extract provides a molecular basis for its observed effects. In silico studies further support the view that these phytoestrogens may preferentially interact with ER beta rather than ER alpha. Quercetin, in particular, demonstrated the highest binding efficacy with ER beta, suggesting its potential role in mediating the anticancer effects observed in TNBC cells. Further research is warranted to explore the full therapeutic potential of phytoestrogens in breast cancer treatment.