Catalpol induces apoptosis in breast cancer in vitro and in vivo: Involvement of mitochondria apoptosis pathway and post-translational modifications.

Breast cancer is a fatal cancer with the highest mortality in female. New strategies for anti-breast cancer are still urgently needed. Catalpol, an iridoid glycoside extracted from the traditional Chinese medicinal plant Rehmannia glutinosa, has shown anticancer efficacy in various cancer cells. However, its effect on breast cancer remains unclear. In this study, we aim to investigate the anti-breast cancer activity of catalpol and elucidate its underlying mechanism. Cell counting kit-8 (CCK-8) and morphology change showed that catalpol could inhibit the proliferation and viability of MCF-7 cells. Catalpol administration reduced the tumor volume in xenograft model. Catalpol induced apoptosis in MCF-7 cells confirmed by Hoechst 33342 staining and Annexin V-FITC/PI double staining. In vivo, catalpol also induced apoptosis as seen from the increased level of terminal-deoxynucleoitidyl transferase mediated nick end labeling (TUNEL) in tumor. According to JC-1 and Dichlorodi-hydrofluorescein Diacetate (DCFH-DA) staining, loss of mitochondrial membrane potential (MMP) and reactive oxygen species (ROS) generation was found in MCF-7 cells treated with catalpol. Furthermore, catalpol also increased the level of cytoplasmic cytochrome c and activity of caspase-3 in MCF-7 cells. Likewise, histopathological and immunohistochemical (IHC) assay also found that catalpol enhanced the levels of cytochrome c and caspase-3 in breast cancer tissues. Ultimately, acetylation, 2-hydroxyisobutyrylation and lactylation were dramatically increased, whereas succinylation, malonylation and phosphorylation were markedly decreased in the breast cancer tumor treated with catalpol. Taken together, catalpol inhibited breast cancer in vitro and in vivo through induction of apoptosis via mitochondria apoptosis pathway and regulation of protein post-translational modifications (PTMs). Thus, it can be considered as an excellent candidate compound for treatment of breast cancer.

Matrine exerts anti­breast cancer activity by mediating apoptosis and protective autophagy via the AKT/mTOR pathway in MCF­7 cells.

Matrine, a major alkaloid isolated from the traditional Chinese herb Sophora flavescens, has been used clinically to treat breast cancer in China. However, the effects of matrine on apoptosis and autophagy in breast cancer cells remain unclear. In the present study, the anti­breast cancer capacity of matrine was evaluated and its role in regulating apoptosis and autophagy in vitro was investigated. Matrine significantly inhibited the growth of MCF­7 cells. In addition, Hoechst 33342 staining and Annexin V/propidium iodide staining demonstrated that incubation with matrine induced apoptosis in MCF­7 cells. Furthermore, matrine induced autophagy in MCF­7 cells, manifesting as an accumulation of light chain 3 II and downregulation of p62. Additionally, matrine suppressed AKT and mammalian target of rapamycin (mTOR) phosphorylation, indicating that the AKT/mTOR pathway is involved in matrine­induced apoptosis and autophagy. Overall, the results of the present study indicated that matrine possesses anti­breast cancer activity by providing protective autophagy via inhibition of the AKT/mTOR pathway. These findings indicated that matrine may be a promising candidate for drug development targeting breast cancer.