Rhabdastrellic acid-A induced autophagy-associated cell death through blocking Akt pathway in human cancer cells.

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.

• Authors: 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, Xiao-Feng Zhu
• Journal: PloS one (PLoS One) Vol. 5 Issue 8 Pg. e12176 (Aug 17 2010) ISSN: 1932-6203 [Electronic] United States
• PMID: 20808909 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• MAP1LC3A protein, human
• Microtubule-Associated Proteins
• Triterpenes
• rhabdastrellic acid A
• Proto-Oncogene Proteins c-akt

Topics

• Autophagy (drug effects)
• Cell Line, Tumor
• Gene Expression Regulation, Neoplastic (drug effects)
• Humans
• Microtubule-Associated Proteins (metabolism)
• Proto-Oncogene Proteins c-akt (metabolism)
• Signal Transduction (drug effects)
• Triterpenes (pharmacology)