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

• Published in: PloS one 2010-08, Vol.5 (8), p.e12176
• Main Authors: Li, Dan-Dan, Guo, Jing-Feng, Huang, Jia-Jia, Wang, Lin-Lin, Deng, Rong, Liu, Jian-Nan, Feng, Gong-Kan, Xiao, Ding-Jun, Deng, Song-Zhi, Zhang, Xiao-Shi, Zhu, Xiao-Feng
• Format: Article
• Language: English
• Subjects: Acids; AKT protein; Anticancer properties; Apoptosis; Autophagy; Autophagy - drug effects; B cells; Biochemistry; Biotechnology; Breast cancer; Cancer; Cancer cells; Cancer therapies; Caspase; Cell Biology/Cell Signaling; Cell death; Cell Line, Tumor; Cytokines; Cytotoxicity; Endothelium; Gene Expression Regulation, Neoplastic - drug effects; Growth factors; Homeostasis; Humans; Investigations; Kinases; Laboratories; Metabolism; Microtubule-Associated Proteins - metabolism; Mortality; Oncology; Oncology/Oncology Agents; Pathogenesis; Phagocytosis; Proteins; Proteolysis; Proto-Oncogene Proteins c-akt - metabolism; Regulation; Rhabdastrella; Signal Transduction - drug effects; Transfection; Triterpenes - pharmacology; Tumor cell lines; Tumorigenesis
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0012176

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. 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. 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.