Cyclovirobuxine D Induces Autophagy-Associated Cell Death via the Akt/mTOR Pathway in MCF-7 Human Breast Cancer Cells

Journal of Pharmacological Sciences

Jiantao Ye¹  Si Gao¹  Jing Lu¹  Ying Gao¹  Peiqing Liu¹  Duanping Sun¹ 

[1] Department of Pharmacology and Toxicology, School of Pharmaceutical Sciences, Sun Yat-Sen University, China

关键词: cyclovirobuxine D;    autophagy;    breast cancer;    Akt;    mTOR;   

DOI  :  10.1254/jphs.14013FP

学科分类：药学

来源: Nihon Yakuri Gakkai Henshuubu / Japanese Pharmacological Society

【 摘 要 】

References(39)Cited-By(10)Autophagy is a highly regulated and multi-step biological process that serves to remove damaged cytoplasmic components and organelles. It has been suggested that the activation of autophagy may be a promising therapeutic strategy for cancer treatment by triggering cell death. In this study, we reported that cyclovirobuxine D (CVB-D), an alkaloid component in a traditional Chinese herb, could induce autophagy in the MCF-7 human breast cancer cell line. CVB-D inhibited the viability of MCF-7 cells in a concentration- and time-dependent manner. Activation of autophagy was characterized by transmission electron microscopy, monodansylcadaverine staining, and expression of autophagy marker microtubule-associated protein 1 light chain 3 (LC3). After CVB-D treatment, a clear accumulation of autophagosomes was observed accompanied with elevated LC3 fluorescent puncta. Western blot analysis revealed that CVB-D significantly promoted the conversion from LC3-I to LC3-II and the expression of autophagy-related protein 5 (ATG5), which are both essential for autophagosome formation. On the other hand, CVB-D–induced autophagy and decrease in cell viability could be blocked by 3-methyladenine, a well-established autophagy inhibitor. Moreover, CVB-D attenuated the phosphorylation of Akt and mTOR, two pivotal suppressors in autophagy pathways. These findings shed new light on the pharmacological actions and mechanism of CVB-D and may support the potential utility of autophagy inducers in cancer treatment.

【 授权许可】

Unknown