title: Galangin inhibits proliferation of hepatocellular carcinoma cells by inducing endoplasmic reticulum stress.
abstract: Prolonged endoplasmic reticulum (ER) stress may activate apoptotic pathways in cancer cells. It is suggested that ER stress has the potential of enhancing tumor death in cancer therapy. Galangin, a flavonol derived from Alpinia officinarum Hance, has been shown to suppress the proliferation of hepatocellular carcinoma cells (HCC). The aim of this study was to determine whether galangin was able to induce ER stress in HepG2, Hep3B and PLC/PRF/5 cells. The proliferation of HCC was tested by MTT method. Intracellular Ca(2+) levels were measured with Fluo3-AM.The proteins levels of GRP94, GRP78 and CHOP were detected by Western blot. To further understand the anti-HCC mechanism of galangin, mitogen-activated protein kinases (MAPKs) were detected. The results showed that galangin treatment induced ER stress was evidenced by increased protein levels of GRP94, GRP78 and CHOP, as well as increased free cytosolic Ca(2+) concentration. ER stress inhibitor 4-PBA and CHOP siRNA blocked significantly galangin-induced ER in all three cell lines. Further experiments showed that MAPKs involved in ER stress induced by galangin. In summary, galangin is identified as a stimulator of ER stress to suppress the proliferation of HCC, and may be used as a potential anti-cancer agent.
authors.affiliation: Department of Biochemistry and Molecular Biology, Guangdong Medical College, Dongguan, Guangdong 523808, China.
authors.forename: Lijuan
authors.initials: L
authors.lastname: Su
authors.forename: Xiaoyi
authors.initials: X
authors.lastname: Chen
authors.forename: Jun
authors.initials: J
authors.lastname: Wu
authors.forename: Biyun
authors.initials: B
authors.lastname: Lin
authors.forename: Haitao
authors.initials: H
authors.lastname: Zhang
authors.forename: Liubo
authors.initials: L
authors.lastname: Lan
authors.forename: Hui
authors.initials: H
authors.lastname: Luo
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D002082:Butylamines / Q000494:pharmacology; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy* / Q000473:pathology; D045744:Cell Line, Tumor / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D000091342:Endoplasmic Reticulum Chaperone BiP; D059865:Endoplasmic Reticulum Stress / Q000187:drug effects*; D005419:Flavonoids / Q000494:pharmacology*; D006360:Heat-Shock Proteins / Q000378:metabolism; D056945:Hep G2 Cells / Q000187:drug effects; D006801:Humans; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000473:pathology; D048670:MAP Kinase Kinase 4 / Q000378:metabolism; D008562:Membrane Glycoproteins / Q000378:metabolism; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D051742:Transcription Factor CHOP / Q000235:genetics / Q000378:metabolism
chemical_list: C121358:4-phenylbutylamine; D000970:Antineoplastic Agents; D002082:Butylamines; C497249:DDIT3 protein, human; D000091342:Endoplasmic Reticulum Chaperone BiP; D005419:Flavonoids; C000717247:HSPA5 protein, human; D006360:Heat-Shock Proteins; D008562:Membrane Glycoproteins; C053387:endoplasmin; C037032:galangin; D051742:Transcription Factor CHOP; D020928:Mitogen-Activated Protein Kinases; D048670:MAP Kinase Kinase 4
keywords: CHOP; ER stress; Galangin; Hepatocellular carcinoma cells; MAPK