title: Myricetin induces apoptosis in HepG2 cells through Akt/p70S6K/bad signaling and mitochondrial apoptotic pathway.
abstract: The present investigation was undertaken to gain insight into the molecular mechanism by which myricetin induces apoptosis in human hepatocarcinoma HepG2 cells. Myricetin caused the disruption of mitochondrial membrane potential in a dose-dependent manner. Moreover, myricetin triggered translocation of the pro-apoptotic protein Bax to the mitochondria, downregulation of anti-apoptotic Bcl-2 expression and upregulated the expression of pro-apoptotic protein Bad in the mitochondria. The present study also showed that myricetin promoted the release of cytochrome C from mitochondria into the cytosol followed by an increase in the proteolytic activation of caspase-3 and the concomitant degradation of PARP protein. Additionally, western blot analysis showed that the Akt/p70s6k1 pathway was inhibited in myricetin-treated HepG2 cells, accordingly the phosphorylation of Bad at Ser136 was downregulated. Collectively, these findings indicate that myricetin induced apoptosis in HepG2 cell through mitochondria apoptotic pathway and Akt/p70s6k1/Bad signaling. Present results provide new information on the possible mechanisms for the anti-cancer activity of myricetin.
authors: Xiao-Hong
authors: XH
authors: Zhang
authors: Shi-Yong
authors: SY
authors: Chen
authors: Lin
authors: L
authors: Tang
authors: Ying-Zhuo
authors: YZ
authors: Shen
authors: Lin
authors: L
authors: Luo
authors: Chen-Wei
authors: CW
authors: Xu
authors: Qiong
authors: Q
authors: Liu
authors: Department of Food Science and Nutrition, School of Biosystems Engineering and Food Science, Zhejiang University, YuHangTang Road 388, Hangzhou 310029, China. duoli@zju.edu.cn.
authors: Duo
authors: D
authors: Li
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D053148:Caspase 3 / Q000235:genetics / Q000378:metabolism; D045304:Cytochromes c / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005419:Flavonoids / Q000494:pharmacology*; D015972:Gene Expression Regulation, Neoplastic; D056945:Hep G2 Cells; D006801:Humans; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism; D011065:Poly(ADP-ribose) Polymerases / Q000235:genetics / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics* / Q000378:metabolism; D038762:Ribosomal Protein S6 Kinases, 70-kDa / Q000235:genetics* / Q000378:metabolism; D015398:Signal Transduction; D051028:bcl-2-Associated X Protein / Q000235:genetics / Q000378:metabolism; D051025:bcl-Associated Death Protein / Q000235:genetics* / Q000378:metabolism
chemical_list: D000972:Antineoplastic Agents, Phytogenic; C494819:BAD protein, human; C494826:BAX protein, human; D005419:Flavonoids; D051028:bcl-2-Associated X Protein; D051025:bcl-Associated Death Protein; C040015:myricetin; D045304:Cytochromes c; D011065:Poly(ADP-ribose) Polymerases; D051057:Proto-Oncogene Proteins c-akt; D038762:Ribosomal Protein S6 Kinases, 70-kDa; D053148:Caspase 3