Rhabdastrellic acid-A induced autophagy-associated cell death through blocking Akt pathway in human cancer cells.
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.
Li
Dan-Dan
DD
State Key Laboratory of Oncology in South China, Cancer Center, Sun Yat-Sen University, Guangzhou, China.
Guo
Jing-Feng
JF
Huang
Jia-Jia
JJ
Wang
Lin-Lin
LL
Deng
Rong
R
Liu
Jian-Nan
JN
Feng
Gong-Kan
GK
Xiao
Ding-Jun
DJ
Deng
Song-Zhi
SZ
Zhang
Xiao-Shi
XS
Zhu
Xiao-Feng
XF
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*
C477012:MAP1LC3A protein, human; D008869:Microtubule-Associated Proteins; D014315:Triterpenes; C529429:rhabdastrellic acid A; D051057:Proto-Oncogene Proteins c-akt
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