Cyclovirobuxine D induces autophagy-associated cell death via the Akt/mTOR pathway in MCF-7 human breast cancer cells.

Abstract

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.

• Authors: Jing Lu, Duanping Sun, Si Gao, Ying Gao, Jiantao Ye, Peiqing Liu
• Journal: Journal of pharmacological sciences (J Pharmacol Sci) Vol. 125 Issue 1 Pg. 74-82 ( 2014) ISSN: 1347-8648 [Electronic] Japan
• PMID: 24758922 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• ATG5 protein, human
• Autophagy-Related Protein 5
• Drugs, Chinese Herbal
• MAP1LC3A protein, human
• Microtubule-Associated Proteins
• 3-methyladenine
• cyclovirobuxine D
• Proto-Oncogene Proteins c-akt
• TOR Serine-Threonine Kinases
• Adenine

Topics

• Adenine (analogs & derivatives, pharmacology)
• Autophagy (drug effects, genetics)
• Autophagy-Related Protein 5
• Breast Neoplasms (drug therapy, genetics, pathology)
• Cell Survival (drug effects)
• Dose-Response Relationship, Drug
• Drugs, Chinese Herbal (chemistry, pharmacology, therapeutic use)
• Female
• Humans
• MCF-7 Cells
• Microtubule-Associated Proteins (metabolism)
• Molecular Targeted Therapy
• Phosphorylation (drug effects)
• Phytotherapy
• Proto-Oncogene Proteins c-akt (metabolism)
• Signal Transduction (drug effects, genetics, physiology)
• TOR Serine-Threonine Kinases (metabolism)