title: Suppression of E-cadherin mediates gallotannin induced apoptosis in Hep G2 hepatocelluar carcinoma cells.
abstract: Though gallotannin was known to have anti-oxidant and antitumor activity, the underlying antitumor mechanism of gallotannin still remains unclear. Thus, in the present study, antitumor mechanism of gallotannin was elucidated in hepatocellular carcinoma cells. Gallotannin significantly exerted cytotoxicity against Hep G2 and Chang hepatocellular carcinoma cells with the accumulation of the sub-G1 population and increase of terminal deoxynucleotidyltransferasedUTP nick end labeling (TUNEL) positive cells as an apoptotic feature. Also, gallotannin attenuated the expression of pro-caspase9, pro-caspase3, Bcl2 and integrin β1 and cleaved poly(ADP)-ribose polymerase (PARP) in Hep G2 and Chang cancer cells. Furthermore, gallotannin suppressed cell repair motility by wound healing assay and also inhibited cell adhesion in Hep G2 cells. Of note, gallotannin attenuated the expression of epithelial cadherin (E-cadherin) to form cell-cell adhesion from the early stage, and also beta-catenin at late phase in Hep G2 cells. Consistently, Immunofluorescence assay showed that E-cadherin or β-catenin expression was suppressed in a time dependent manner by gallotannin. Furthermore, silencing of E-cadherin by siRNA transfection method enhanced PAPR cleavage, caspase 3 activation and sub G1 population and attenuated the cell adhesion induced by gallotannin in Hep G2 cells. Overall, our findings demonstrate that the disruption of cell adhesion junction by suppression of E-cadherin mediates gallotannin enhanced apoptosis in Hep G2 liver cancer cells.
authors.affiliation: 2. Graduate School of East-West Medical Science, Kyung Hee University, Yongin 449-701, Republic of Korea.
authors.forename: Hee Jeong
authors.initials: HJ
authors.lastname: Han
authors.affiliation: 1. College of Korean Medicine, Kyung Hee University, 1 Hoegi-dong, Dongdaemun-gu, Seoul 131-701, Republic of Korea;
authors.forename: Hee Young
authors.initials: HY
authors.lastname: Kwon
authors.affiliation: 1. College of Korean Medicine, Kyung Hee University, 1 Hoegi-dong, Dongdaemun-gu, Seoul 131-701, Republic of Korea;
authors.forename: Eun Jung
authors.initials: EJ
authors.lastname: Sohn
authors.affiliation: 1. College of Korean Medicine, Kyung Hee University, 1 Hoegi-dong, Dongdaemun-gu, Seoul 131-701, Republic of Korea;
authors.forename: Hyunsuk
authors.initials: H
authors.lastname: Ko
authors.affiliation: 2. Graduate School of East-West Medical Science, Kyung Hee University, Yongin 449-701, Republic of Korea.
authors.forename: Bogeun
authors.initials: B
authors.lastname: Kim
authors.affiliation: 1. College of Korean Medicine, Kyung Hee University, 1 Hoegi-dong, Dongdaemun-gu, Seoul 131-701, Republic of Korea;
authors.forename: Kwon
authors.initials: K
authors.lastname: Jung
authors.affiliation: 2. Graduate School of East-West Medical Science, Kyung Hee University, Yongin 449-701, Republic of Korea.
authors.forename: Jae Hwan
authors.initials: JH
authors.lastname: Lew
authors.affiliation: 1. College of Korean Medicine, Kyung Hee University, 1 Hoegi-dong, Dongdaemun-gu, Seoul 131-701, Republic of Korea;
authors.forename: Sung-Hoon
authors.initials: SH
authors.lastname: Kim
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology*; D015820:Cadherins / Q000378:metabolism*; D006528:Carcinoma, Hepatocellular / Q000378:metabolism / Q000503:physiopathology*; D005455:Fluorescent Antibody Technique; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D056945:Hep G2 Cells / Q000378:metabolism / Q000502:physiology*; D006801:Humans; D047348:Hydrolyzable Tannins / Q000494:pharmacology*; D020287:In Situ Nick-End Labeling; D008113:Liver Neoplasms / Q000378:metabolism / Q000503:physiopathology*; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000235:genetics
chemical_list: D000970:Antineoplastic Agents; D015820:Cadherins; D047348:Hydrolyzable Tannins; D034741:RNA, Small Interfering; D011065:Poly(ADP-ribose) Polymerases
keywords: E-cadherin.; Hep G2 cells; PARP; apoptosis; caspase; gallotannin