Molecular Mechanism Of Ginsenoside-Rh2-induced Apoptosis In Triple-negative Breast Cancer Cell MDA-MB-231

Breast cancer is the most malignant tumor, it is the second leading cause of deathamong women. Every year more than1,000,000women develop to breast cancer, andpatients of breast cancer are becoming younger. Treatment of breast cancer is still aproblem of the medical profession. Currently, the main treatment is through earlydetection of breast cancer and breast surgery-based treatment. But this treatment is nota timely treatment for all patients, meanwhile, female breast removal would be a hugephysical and psychological torture to women. Thus, looking for pharmaceuticallyeffective drug to cure breast cancer and making clear of the mechanism is veryimportant.MDA-MB-231is a kind of triple-negative breast cancer cells (TNBC), lack ofestrogen receptor (ER), progesterone receptor (PR) and human epidermal growthfactor receptor (HER2). It is a kind of vicious high degree of breast cancer cells. Aswe all know, ER, PR, HER2are important targets for the clinical treatment of breastcancer. Due to the lack of these targets, TNBC patients can’t be performed normalendocrine therapy and targeted therapy, leading to a poor prognosis, recurrence rate,high transfer rate and high mortality. Therefore, the treatment of triple-negative breastcancer has become the focus of the current study.Ginsenoside-Rh2is a small amount of the active ingredients in ginseng. Accordingto their optical activity, Ginsenoside-Rh2can be divided into20(S)-Rh2and20(R)-Rh2. It has been reported that Ginsenoside-Rh2and its derivatives can inhibitthe growth of a variety of tumors, such as: ovarian cancer, pancreatic cancer, prostatecancer, and so on. Ginsenoside-Rh2can also inhibit cancer cell migration andinvasion, effectively inhibit tumor growth.In this study, we focus on clarify the inhibition of proliferation effect ofGinsenoside-Rh2on triple negative breast cancer cell line MDA-MB-231and itsmolecular mechanism.Through this research, we found that:a)20(S)-Rh2could effectively inhibit the proliferation of MDA-MB-231cells, andthe IC50is3.92g/mL.20(R)-Rh2showed minor growth inhibition inMDA-MB-231cells (IC50＞100g/mL)；b)20(S)-Rh2induces apoptosis in triple-negative breast cancer cells(MDA-MB-231)；c)20(S)-Rh2-induced apoptosis in triple-negative breast cancer cells (MDA-MB-231) is via activation of mitochondrial apoptosis pathway；d)20(S)-Rh2-induced apoptosis in triple-negative breast cancer cells(MDA-MB-231) can magnify the apoptotic signal through the degradation ofc-IAP2；e)20(S)-Rh2-induced apoptosis in triple-negative breast cancer cells(MDA-MB-231) does not activate the death receptor apoptosis pathway；Above all,20(S)-Rh2can trigger the translocation of Bax to themitochondria, resulting in mitochondrial membrane potential (MMP)depolarization and the subsequent release of cytochrome c as well as the secondmitochondria-derived activator of caspase (Smac) into the cytosol. Smac caninteract with anti-apoptotic protein c-IAP2and trigger the degradation of c-IAP2in order to magnify the apoptotic signal. Meanwhile, we haven’t detect theactivation of Caspase-8, an initiator caspase that is required to activate themembrane receptor-mediated extrinsic apoptosis pathway. Since p53in triplenegative breast cancer cells MDA-MB-231is mutant, the mutation point isarginine280of the p53, locus in the DNA-binding domain, directly affect itstranscriptional activity. Therefore,20(S)-Rh2could not induce caspase-8activation via p53-dependent Fas expression.