title: Galangin inhibits proliferation of HepG2 cells by activating AMPK via increasing the AMP/TAN ratio in a LKB1-independent manner.
abstract: Galangin, a flavonol derived from Alpinia officinarum Hance and used as food additives in southern China, induces apoptosis and autophagy to suppress the proliferation of HepG2 cells. In this study, we demonstrated that galangin induced autophagy by increasing the ratio of AMP/TAN in HepG2 cells. It stimulated the phosphorylation of adenosine monophosphate-activated protein kinase (AMPK) and LKB1, but inhibited the phosphorylation of AKT and mTOR. Inhibition of AMPK activation suppressed the dephosphorylation of mTOR to block galangin-induced autophagy. AMPK activation by galangin appeared to be independent of the LKB1 signaling pathway because the down-regulation of LKB1 by its siRNA failed to affect galangin-induced autophagy. Collectively, the findings demonstrated a novel mechanism of how galangin induces autophagy via activating AMPK in a LKB1- independent manner. The induction of autophagy can thus reflect the anti-proliferation effect of galangin in HCC cells.
authors.affiliation: Department of Biochemistry and Molecular Biology, Guangdong Medical College, Dongguan, Guangdong, 523808, China. Electronic address: taohaizhang@tom.com.
authors.forename: Haitao
authors.initials: H
authors.lastname: Zhang
authors.forename: Ning
authors.initials: N
authors.lastname: Li
authors.forename: Jun
authors.initials: J
authors.lastname: Wu
authors.forename: Lijuan
authors.initials: L
authors.lastname: Su
authors.forename: Xiaoyi
authors.initials: X
authors.lastname: Chen
authors.forename: Biyun
authors.initials: B
authors.lastname: Lin
authors.forename: Hui
authors.initials: H
authors.lastname: Luo
mesh_terms: D000091162:AMP-Activated Protein Kinase Kinases; D055372:AMP-Activated Protein Kinases / Q000378:metabolism*; D000249:Adenosine Monophosphate / Q000378:metabolism*; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D001343:Autophagy / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D004789:Enzyme Activation / Q000187:drug effects; D005260:Female; D005419:Flavonoids / Q000494:pharmacology*; D056945:Hep G2 Cells; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D017346:Protein Serine-Threonine Kinases / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000235:genetics; D023041:Xenograft Model Antitumor Assays
chemical_list: D000970:Antineoplastic Agents; D005419:Flavonoids; D034741:RNA, Small Interfering; C037032:galangin; D000249:Adenosine Monophosphate; D017346:Protein Serine-Threonine Kinases; C109790:STK11 protein, human; D000091162:AMP-Activated Protein Kinase Kinases; D055372:AMP-Activated Protein Kinases
keywords: AMPK; Autophagy; Galangin; LKB1; mTOR