title: Galangin induces apoptosis in hepatocellular carcinoma cells through the caspase 8/t-Bid mitochondrial pathway.
abstract: This study has investigated whether galangin, a flavonol derived from Alpinia officinarum Hance and used as food additives in southern China, induces apoptosis in hepatocellular carcinoma cells (HCCs) by activation of the caspase-8 and Bid pathway. The apoptosis of HCCs was evaluated by in situ uptake of propidium iodide and Hoechst 33258. Protein expressions were detected by Western blotting. Caspase-8 activity was measured using colorimetric method. To confirm the galangin-induced apoptotic pathway, inhibition of caspase-8 activity by Z-IETD-FMK, knockdown of Bid expression with siRNA, and overexpression of Bcl-2 in cells were carried out, respectively. The results show that galangin has significantly induced apoptosis in HCC lines. The caspase-8 is activated, and the cleavage of Bid results in the increase in tBid. The galangin-induced apoptosis is attenuated by Z-IETD-FMK, Bid siRNA, and Bcl-2 overexpression, respectively. However, Bcl-2 fails to suppress caspase-8 activation and the cleavage of Bid. This study has demonstrated that galangin induces apoptosis in HCCs by activating caspase 8/t-Bid mitochondrial pathway. Although Bcl-2 overexpression attenuates galangin-mediated apoptosis of HCCs, it is not mediated by the inhibition of tBid generation and caspase-8 activation.
authors.affiliation: Department of Biochemistry and Molecular Biology, Guangdong Medical College, Zhanjiang, 524023, China. taohaizhang@tom.com
authors.forename: Hai-Tao
authors.initials: HT
authors.lastname: Zhang
authors.forename: Jun
authors.initials: J
authors.lastname: Wu
authors.forename: Min
authors.initials: M
authors.lastname: Wen
authors.forename: Li-Juan
authors.initials: LJ
authors.lastname: Su
authors.forename: Hui
authors.initials: H
authors.lastname: Luo
mesh_terms: D032429:Alpinia / Q000737:chemistry; D017209:Apoptosis / Q000187:drug effects*; D015153:Blotting, Western; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D053181:Caspase 8 / Q000032:analysis / Q000378:metabolism*; D005419:Flavonoids / Q000494:pharmacology* / Q000627:therapeutic use; D056945:Hep G2 Cells; D006801:Humans; D008099:Liver / Q000378:metabolism; D009842:Oligopeptides / Q000494:pharmacology; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000378:metabolism; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism
chemical_list: D005419:Flavonoids; D009842:Oligopeptides; D019253:Proto-Oncogene Proteins c-bcl-2; D034741:RNA, Small Interfering; C403753:benzyloxycarbonyl-isoleucyl-glutamyl-threonyl-aspartic acid fluoromethyl ketone; C037032:galangin; D053181:Caspase 8