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

Abstract

BackgroundSaraca asoca (Asoka) is reported to possess phytoestrogenic components with anticancer properties. The phytoestrogens are recognized as natural agonists for ERβ, which acts as an antagonist to ERα. Despite the absence of ERα, studies have identified ERβ 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 ERα and β.ResultsThe extract of Asoka was found to be cytotoxic against TNBC cell line, MDAMB-231 with IC50 of 70.22 ± 1.89 μg/mL and towards HER+ breast cancer cell line, SKBR3 with IC50 of 98.41 ± 2.31 μg/mL, respectively. Whereas the extract did not show any cytotoxicity towards ERα cell line, MCF-7 even up to the concentration 300 μg/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 β-sitosterol, quercetin, kaempferol and others. The docking results revealed good binding efficacy of phytoestrogens with ERβ than ERα 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.ConclusionThe 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 β-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 ERβ rather than ERα. Quercetin, in particular, demonstrated the highest binding efficacy with ERβ, 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.