Journal
JOURNAL OF PHARMACOLOGICAL SCIENCES
Volume 125, Issue 1, Pages 74-82Publisher
JAPANESE PHARMACOLOGICAL SOC
DOI: 10.1254/jphs.14013FP
Keywords
cyclovirobuxine D; autophagy; breast cancer; Akt; mTOR
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Funding
- National Natural Science Foundation of China [81072641, 81273499, 81200096]
- National Science and Technology Major Project of China Key New Drug Creation and Manufacturing Program [2011ZX09401-307]
- Team item of Natural Science Foundation of Guangdong Province [S2011030003190]
- Major Project of Department of Education of Guangdong Province [CXZD1006]
- Guangdong Science Foundation [2012A080201007]
- Major Project of Guangzhou City [2011Y1-00017]
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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.
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