1. Rhabdastrellic Acid-A Induced Autophagy-Associated Cell Death through Blocking Akt Pathway in Human Cancer Cells.
- Author
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Dan-Dan Li, Jing-Feng Guo, Jia-Jia Huang, Lin-Lin Wang, Rong Deng, Jian-Nan Liu, Gong-Kan Feng, Ding-Jun Xiao, Song-Zhi Deng, Xiao-Shi Zhang, and Xiao-Feng Zhu
- Subjects
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CELL death , *CANCER cells , *CYSTS (Pathology) , *CELL lines , *GENE transfection , *ANTINEOPLASTIC agents , *CYTOCHROMES , *CARCINOGENESIS , *THERAPEUTICS ,TUMOR prevention - Abstract
Background: Autophagy is an evolutionarily conserved protein degradation pathway. A defect in autophagy may contribute to tumorigenesis. Autophagy inducers could have a potential function in tumor prevention and treatment. Methodology/Principal Findings: Our results showed that Rhabdastrellic acid-A, an isomalabaricane triterpenoid isolated from the sponge Rhabdastrella globostellata, inhibited proliferation of human cancer cell lines Hep3B and A549 and induced caspase-independent cell death in both the cell lines. Further investigation showed that Rhabdastrellic acid-A induced autophagy of cancer cells determined by YFP-LC3 punctation and increased LC3-II. The pretreatment with autophagy inhibitor 3-MA inhibited Rhabdastrellic acid-A-induced cell death. Knockdown of autophagy-related gene Atg5 inhibited Rhabdastrellic acid-A-induced cell death in A549 cells. Also, phospho-Akt and its downstream targets significantly decreased after treatment with Rhabdastrellic acid-A in both cancer cell lines. Transfection of constitutive active Akt plasmid abrogated autophagy and cell death induced by Rhabdastrellic acid-A. Conclusions/Significance: These results suggest that Rhabdastrellic acid-A could induce autophagy-associated cell death through blocking Akt pathway in cancer cells. It also provides the evidence that Rhabdastrellic acid-A deserves further investigation as a potential anticancer or cancer preventive agent. [ABSTRACT FROM AUTHOR]
- Published
- 2010
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