title: Galangin suppresses HepG2 cell proliferation by activating the TGF-β receptor/Smad pathway.
abstract: Galangin can suppress hepatocellular carcinoma (HCC) cell proliferation. In this study, we demonstrated that galangin induced autophagy by activating the transforming growth factor (TGF)-β receptor/Smad pathway and increased TGF-β receptor I (RI), TGF-βRII, Smad1, Smad2, Smad3 and Smad4 levels but decreased Smad6 and Smad7 levels. Autophagy induced by galangin appears to depend on the TGF-β receptor/Smad signalling pathway because the down-regulation of Smad4 by siRNA or inhibition of TGF-β receptor activation by LY2109761 blocked galangin-induced autophagy. The down-regulation of Beclin1, autophagy-related gene (ATG) 16L, ATG12 and ATG3 restored HepG2 cell proliferation and prevented galangin-induced apoptosis. Our findings indicate a novel mechanism for galangin-induced autophagy via activation of the TGF-β receptor/Smad pathway. The induction of autophagy thus reflects the anti-proliferation effect of galangin on HCC cells.
authors.affiliation: Department of Biochemistry and Molecular Biology, Guangdong Medical College, Dongguan, Guangdong 523808, China; Affiliated Hospital of Guangdong Medical College, Zhanjiang, Guangdong 524001, China.
authors.forename: Yajun
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Affiliated Hospital of Guangdong Medical College, Zhanjiang, Guangdong 524001, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Wu
authors.affiliation: Department of Biochemistry and Molecular Biology, Guangdong Medical College, Dongguan, Guangdong 523808, China.
authors.forename: Biyun
authors.initials: B
authors.lastname: Lin
authors.affiliation: Department of Biochemistry and Molecular Biology, Guangdong Medical College, Dongguan, Guangdong 523808, China.
authors.forename: Xv
authors.initials: X
authors.lastname: Li
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.affiliation: Department of Biochemistry and Molecular Biology, Guangdong Medical College, Dongguan, Guangdong 523808, China.
authors.forename: Hang
authors.initials: H
authors.lastname: Ding
authors.affiliation: Department of Biochemistry and Molecular Biology, Guangdong Medical College, Dongguan, Guangdong 523808, China.
authors.forename: Xiaoyi
authors.initials: X
authors.lastname: Chen
authors.affiliation: Department of Biochemistry and Molecular Biology, Guangdong Medical College, Dongguan, Guangdong 523808, China.
authors.forename: Liubo
authors.initials: L
authors.lastname: Lan
authors.affiliation: Department of Chemistry, Guangdong Medical College, Zhanjiang, Guangdong 524023, China. Electronic address: luohui@gdmc.edu.cn.
authors.forename: Hui
authors.initials: H
authors.lastname: Luo
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism; D001343:Autophagy / Q000187:drug effects; D006528:Carcinoma, Hepatocellular / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D049109:Cell Proliferation / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D005419:Flavonoids / Q000494:pharmacology*; D056945:Hep G2 Cells; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D011720:Pyrazoles / Q000494:pharmacology; D011758:Pyrroles / Q000494:pharmacology; D034622:RNA Interference; D000077293:Receptor, Transforming Growth Factor-beta Type I; D000077294:Receptor, Transforming Growth Factor-beta Type II; D018125:Receptors, Transforming Growth Factor beta / Q000037:antagonists & inhibitors / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects*; D051785:Smad Proteins / Q000235:genetics / Q000378:metabolism*; D014162:Transfection; D016212:Transforming Growth Factor beta / Q000378:metabolism*
chemical_list: D000970:Antineoplastic Agents; D051017:Apoptosis Regulatory Proteins; D005419:Flavonoids; C530108:LY2109761; D011720:Pyrazoles; D011758:Pyrroles; D018125:Receptors, Transforming Growth Factor beta; D051785:Smad Proteins; D016212:Transforming Growth Factor beta; C037032:galangin; D017346:Protein Serine-Threonine Kinases; D000077293:Receptor, Transforming Growth Factor-beta Type I; D000077294:Receptor, Transforming Growth Factor-beta Type II
keywords: Autophagy; Autophagy-related gene; Galangin; Smad; TGF-β receptor