In silico and in vitro assessment of anti-proliferative and pro-apoptotic potential of quercetin derivatives on Luminal A breast cancer cells

نویسندگان

1 Department of Biology, ShQ C, Islamic Azad University, Shahr-e Qods, Iran

2 Department of Microbiology, ShQ C, Islamic Azad University, Shahr-e Qods, Iran

3 Department of Biology, ShQ C, Islamic Azad University, Shahr-e Qods, Iran

doi
10.22034/bmmj.2026.729946
چکیده

Anti-hormone therapy is a conventional and established remedy to treat Luminal A breast cancer. Howbeit, about 20–30% of tumors are resistant to hormone therapy. Phytotherapeutic agents have evinced prophylactic and therapeutic capacities in breast carcinomas. Tamarixetin, a natural O-methylated flavonol, exhibited anti-inflammatory, cardiotonic, gastroprotective properties and mediated the suppression multidrug resistance proteins. However, effects of tamarixetin on Luminal A breast cancer are underexplored compared to quercetin. This survey compares the molecular docking of tamarixetin and quercitrin to apoptosis-related proteins. Based on which, the cytotoxicity and apoptosis induction potency of the more favorable flavonoids on MCF-7 cancer cells were assessed. The results displayed relatively higher negative binding energy, and consequently more effective interactions of tamarixetin with p21, p53, Bax, Bcl2 and caspase 8 in comparison to quercitrin. It was found that treatment of MCF-7 cells with tamarixetin engenders a decrease in viability in a time and dose-dependent manner. Tamarixetin-induced apoptosis in MCF-7 cells was evidenced via flowcytometry. Gene expression analysis affirmed that tamarixetin exerted pro-apoptotic potential through activation of the extrinsic pathway of apoptosis via activation of caspase 8, and the intrinsic pathway of apoptosis by stimulation of p53 and it’s essential downstream target, p21. This flavonol enhanced the expression of anti-oxidant enzymes (SOD1 and SOD2) independently, or dependent on p53. Our outcomes propose tamarixetin as an auspicious complementary anti-cancer herbal candidate for therapy of Luminal A breast cancer, worthy of further investigation.