Minecoside promotes apoptotic progression through STAT3 inactivation in breast cancer cells

Abstract

Breast cancer is one of the most common malignant tumors in women worldwide, and is a major cause of mortality and morbidity in cancer patients. Constitutive activation of STAT3 has been found in a variety of malignant tumors, including breast cancer. Since STAT3 activation is capable of regulating various important features of tumor cells, identification of a novel STAT3 inhibitor is considered a potential strategy for treating breast cancer. The aim of the present study was to examine whether minecoside (MIN), an active compound extracted from Veronica peregrina L. , exerts an antitumor effect by inhibiting STAT3 signaling pathway in MDA-MB-231 cells. The results revealed that MIN inhibited the constitutive STAT3 activation in a dose- and time-dependent manner. MIN also blocked the nuclear translocation of STAT3 and suppressed STAT3-DNA binding. In addition, MIN downregulated the STAT3-mediated expression of proteins such as Bcl-xL, Bcl-2, CXCR4, VEGF, and cyclin D1. Subsequently, MIN promoted the caspase-dependent apoptosis in MDA-MB-231 cells. Overall, results of the present study provide evidence that MIN exerted anticancer activity via inhibition of the STAT3 signaling pathway. Further studies using animal models are required to determine the potential of this molecule as an anticancer drug.

β-Caryophyllene Counteracts Chemoresistance Induced by Cigarette Smoke in Triple-Negative Breast Cancer MDA-MB-468 Cells

“…pSTAT3(Tyr705) has been found to be constitutively activated in different breast cancers, especially in triple-negative ones [ 98 ]. Its downregulation has also been associated with a reduced growth of different breast cancer cell subtypes [ 99 , 100 ], thus suggesting an interest in the STAT3 inhibitor as a potential anticancer or adjuvant strategy for breast cancer. Our results highlighted that CSC markedly activated pSTAT3(Tyr705) in MDA-MB-468 cells, but its effect was completely reversed by β-caryophyllene.…”