A comparative study on anti-cancer potentials of the tamarixetin and quercitrin on Luminal A Breast Cancer

Hormone blocking therapy is a conventional and established remedy to treat the more frequent subtype of breast cancers, Luminal A. However, about ۲۰-۳۰% of tumors are resistant to hormone therapy. Phytotherapeutic agents displayed prophylactic and therapeutic roles in breast malignancies. Tamarixetin, a natural O methylated flavonol, exhibited anti inflammatory, cardiotonic, gastroprotective properties and mediated the suppression multi drug resistance proteins. Howbeit, studies on its anticancer potentials are still inadequate. The present survey is a comparative evaluation of the molecular docking of Tamarixetin / Quercitrin to the apoptosis mediated proteins. Based on which, the cytotoxicity and apoptosis induction potency of the more favorable flavonoid, on MCF ۷ cancer cells were assessed. Methods: The in silico interaction of Tamarixetin and Quercitrin apoptosis associated proteins (p۲۱, p۵۳, caspase ۸, bax, and bcl۲) were evaluated by molecular docking. The MCF ۷ cells treated with various concentrations of Tamarixetin (۰-۵۰µg/ml) for ۲۴ and ۴۸ h and cell viability was evaluated by MTT assay. The pro apoptotic potential of Tamarixetin (۲۵µg/ml) for ۲۴ h on MCF ۷ cells were assessed by Annexin V/PI flow cytometry assay. The expression levels of p۵۳, p۲۱, caspase ۸, SOD۱ and SOD۲ were measured by Real time PCR. Results: It was found that treatment of MCF ۷ cells with Tamarixetin engenders a decrease in viability in a time and dose dependent manner. Tamarixetin induced early and late apoptosis in MCF ۷ cells was demonstrated via flowcytometry. Gene expression analysis affirmed that Tamarixetin exerted pro apoptotic potential through activation of the extrinsic pathway of apoptosis via activation of caspase ۸, and the intrinsic pathway of apoptosis by stimulation of p۵۳ and its essential downstream target, p۲۱. This flavonol enhanced the expression of antioxidant enzymes (SOD۱ and SOD۲) independently, or dependent on p۵۳. Conclusion: The findings of this research propose Tamarixetin as an auspicious complementary anticancer herbal medicine for therapy of Luminal A breast cancer.

کلیدواژه ها:

Tamarixetin ، Luminal A ، anti proliferative ، pro apoptotic