title: 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.
  
  
  RESULTS
  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
  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.affiliation: State Key Laboratory of Oncology in South China, Cancer Center, Sun Yat-Sen University, Guangzhou, China.
authors.forename: Dan-Dan
authors.initials: DD
authors.lastname: Li
authors.forename: Jing-Feng
authors.initials: JF
authors.lastname: Guo
authors.forename: Jia-Jia
authors.initials: JJ
authors.lastname: Huang
authors.forename: Lin-Lin
authors.initials: LL
authors.lastname: Wang
authors.forename: Rong
authors.initials: R
authors.lastname: Deng
authors.forename: Jian-Nan
authors.initials: JN
authors.lastname: Liu
authors.forename: Gong-Kan
authors.initials: GK
authors.lastname: Feng
authors.forename: Ding-Jun
authors.initials: DJ
authors.lastname: Xiao
authors.forename: Song-Zhi
authors.initials: SZ
authors.lastname: Deng
authors.forename: Xiao-Shi
authors.initials: XS
authors.lastname: Zhang
authors.forename: Xiao-Feng
authors.initials: XF
authors.lastname: Zhu
mesh_terms: D001343:Autophagy / Q000187:drug effects*; D045744:Cell Line, Tumor; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D008869:Microtubule-Associated Proteins / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects*; D014315:Triterpenes / Q000494:pharmacology*
chemical_list: C477012:MAP1LC3A protein, human; D008869:Microtubule-Associated Proteins; D014315:Triterpenes; C529429:rhabdastrellic acid A; D051057:Proto-Oncogene Proteins c-akt
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