۸-Hydroxydaidzein suppresses breast cancer stem cells to cease breast cancer progression

Introduction: Cancer stem cells (CSCs) have a key role in different stages of cancer development and therapy resistance. ۸-Hydroxydaidzein (۸-OHD) is known as an anti-cancer agent against many tumors. Accordingly, the aim of this study is to evaluate the effects of ۸-OHD on the suppression of breast cancer stem-like cells (BCSCs). Methods: The anti-proliferative and pro-apoptotic properties of ۸-OHD were examined by MTS assay and flowcytometry. The expression levels of stemness markers and JAK۲/STAT۳ proteins were measured by quantitative real time-PCR (qRT-PCR) and western blotting, respectively. Results: ۸-OHD significantly decreased three out of six stemness markers and remarkably reduced viability and induced apoptosis of spheroidal and parental cells compared to controls. Further experiments using CD۹۵L, as a death ligand, and ZB۴ antibody, as an extrinsic apoptotic pathway blocker, showed that ۸-OHD induced apoptosis through the intrinsic pathway, proposing a mechanism by which ۸-OHD triggers apoptosis. Results of western blot analysis also revealed a marked decline in the phosphorylation of JAK۲ and STAT۳ proteins. Conclusion: Our data unraveled the anti-BCSC activity of ۸-OHD by reducing stemness markers, inducing toxicity, and triggering apoptosis of these cells and parental cells. Our results also proposed a novel mechanism by which ۸-OHD stimulated apoptosis of BCSCs.

کلیدواژه ها:

Breast cancer therapy ، JAK۲ ، STAT۳ ، Apoptosis ، Resistance