Coptis chinensis inhibits hepatocellular carcinoma cell growth through nonsteroidal anti-inflammatory drug-activated gene activation.
Conventional chemotherapy of liver cancer fails to provide satisfactory remission and may cause serious side effects, thus it is crucial to derive alternative treatments that effectively inhibit cancer cell growth with known mechanisms of action. In the present study, we investigated the anti-carcinogenic effects of Coptis chinensis and its major constituent, berberine, in HepG2 hepatocellular carcinoma (HCC) cells and attempted to elucidate the underlying mechanism, including involvement of the nonsteroidal anti-inflammatory drug (NSAID)-activated gene (NAG-1). Inhibition of cell proliferation, induction of apoptosis and cell cycle arrest at the G2/M phase were observed in HepG2 cells treated with Coptis chinensis or berberine. The pro-apoptotic effects were associated with corresponding down-regulation of Bcl-2, activation of procaspase-3 and -9 as well as cleavage of poly (ADP-ribose) polymerase. We further demonstrated the involvement of NAG-1 in the pro-apoptotic events following prior activation of its upstream transcriptional factor early growth response gene (Egr-1). This was confirmed by increased NAG-1 promoter activity preceded by the elevation of Egr-1/ DNA binding activity. Our results suggest that both Coptis chinensis and berberine are potential anti-carcinogenic agents in treating HCC by inducing cell cycle arrest and promotion of apoptosis, while NAG-1 is a molecular target during the drug-induced pro-apoptotic action in HepG2 cells.
Auyeung
Kathy Ka-Wai
KK
Pharmacology and Toxicology Laboratory, School of Chinese Medicine, Hong Kong Baptist University, Hong Kong SAR, PR China.
Ko
Joshua Ka-Shun
JK
D016588:Anticarcinogenic Agents / Q000737:chemistry / Q000627:therapeutic use*; D001599:Berberine / Q000737:chemistry / Q000627:therapeutic use*; D015153:Blotting, Western; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy*; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002851:Chromatography, High Pressure Liquid; D039323:Coptis / Q000737:chemistry*; D004365:Drugs, Chinese Herbal / Q000737:chemistry / Q000627:therapeutic use*; D051766:Early Growth Response Protein 1 / Q000378:metabolism; D024202:Electrophoretic Mobility Shift Assay; D005434:Flow Cytometry; D055436:Growth Differentiation Factor 15 / Q000378:metabolism*; D006801:Humans; D008113:Liver Neoplasms / Q000188:drug therapy*; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism
D016588:Anticarcinogenic Agents; D004365:Drugs, Chinese Herbal; D051766:Early Growth Response Protein 1; D055436:Growth Differentiation Factor 15; D019253:Proto-Oncogene Proteins c-bcl-2; D001599:Berberine; D011065:Poly(ADP-ribose) Polymerases