Rhabdastrellic Acid-A Induced Autophagy-Associated Cell Death through Blocking Akt Pathway in Human Cancer Cells 英文参考文献.docVIP

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Rhabdastrellic Acid-A Induced Autophagy-Associated Cell Death through Blocking Akt Pathway in Human Cancer Cells 英文参考文献.doc

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Rhabdastrellic Acid-A Induced Autophagy-Associated Cell Death through Blocking Akt Pathway in Human Cancer Cells 英文参考文献

RhabdastrellicAcid-AInducedAutophagy-Associated CellDeaththroughBlockingAktPathwayinHuman CancerCells Dan-DanLi1.,Jing-FengGuo2.,Jia-JiaHuang1,Lin-LinWang1,RongDeng1,Jian-NanLiu1 ,Gong-Kan Feng1,Ding-JunXiao3,Song-ZhiDeng3,Xiao-ShiZhang1,Xiao-FengZhu1* 1StateKeyLaboratoryofOncologyinSouthChina,CancerCenter,SunYat-SenUniversity,Guangzhou,China,2TheAffiliatedHeXianMemorialHospitalofSouthern MedicalUniversity,Guangzhou,China,3GuangzhouInstituteofChemistry,ChineseAcademyofSciences,Guangzhou,China Abstract Background: Autophagy is an evolutionarily conserved protein degradation pathway. A defect in autophagy may contributetotumorigenesis.Autophagyinducerscouldhaveapotentialfunctionintumorpreventionandtreatment. Methodology/PrincipalFindings:OurresultsshowedthatRhabdastrellicacid-A,anisomalabaricanetriterpenoidisolated 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 autophagyinhibitor3-MAinhibitedRhabdastrellicacid-A-inducedcelldeath.Knockdownofautophagy-relatedgeneAtg5 inhibitedRhabdastrellicacid-A-inducedcelldeathinA549cells.Also,phospho-Aktanditsdownstreamtargetssignificantly decreasedaftertreatmentwithRhabdastrellicacid-Ainbothcancercelllines.TransfectionofconstitutiveactiveAktplasmid abrogatedautophagyandcelldeathinducedbyRhabdastrellicacid-A. Conclusions/Significance: TheseresultssuggestthatRhabdastrellicacid-Acouldinduceautophagy-associatedcelldeath through blocking Akt pathway in cancer cells. It also provides the evidence that Rhabdastrellic acid-A deserves further investigationasapotentialanticancerorcancerpreventiveagent. Citation: Li D-D, Guo J-F, Huang J-J, Wang L-L, Deng R, et al. (2010) Rhabdastrellic Acid-A Induced Autophagy-Associated Cell Death through Blocking