title: Liriodenine inhibits the proliferation of human hepatoma cell lines by blocking cell cycle progression and nitric oxide-mediated activation of p53 expression.
abstract: Liriodenine was isolated from the leaves of Michelia compressa. This study was designed to assess cell cycle arrest, the production of nitric oxide (NO) and p53 expression in liriodenine-treated human hepatoma cell lines, including wild-type p53 (Hep G2 and SK-Hep-1). As evidenced by flowcytometric studies, liriodenine induced cell cycle G(1) arrest and inhibited DNA synthesis in Hep G2 and SK-Hep-1 cell lines. The p53, iNOS expression and intracellular NO level were markedly increased in Hep G2 cells after liriodenine treatment. A NO inhibitor, carboxy-PTIO inhibited the p53 expression induced by liriodenine. In addition, liriodenine could not induce obvious cytotoxicity in normal human IMR-90 cell line. These results demonstrate that NO production and p53 expression are critical factors in liriodenine-induced growth inhibition in human wild-type p53 hepatoma cells.
authors.affiliation: Basic Medical Science Education Center, Fooyin University, Ta-Liao, Kaohsiung Hsien 831, Taiwan, ROC.
authors.forename: Tian-Jye
authors.initials: TJ
authors.lastname: Hsieh
authors.forename: Tsan-Zon
authors.initials: TZ
authors.lastname: Liu
authors.forename: Chi-Liang
authors.initials: CL
authors.lastname: Chern
authors.forename: Der-An
authors.initials: DA
authors.lastname: Tsao
authors.forename: Fung-Jou
authors.initials: FJ
authors.lastname: Lu
authors.forename: Yu-Hua
authors.initials: YH
authors.lastname: Syu
authors.forename: Pei-Ying
authors.initials: PY
authors.lastname: Hsieh
authors.forename: Han-Shu
authors.initials: HS
authors.lastname: Hu
authors.forename: Ting-Ting
authors.initials: TT
authors.lastname: Chang
authors.forename: Ching-Hsein
authors.initials: CH
authors.lastname: Chen
mesh_terms: D000963:Antimetabolites; D000972:Antineoplastic Agents, Phytogenic / Q000737:chemistry / Q000494:pharmacology*; D001060:Aporphines / Q000737:chemistry / Q000494:pharmacology*; D015153:Blotting, Western; D001973:Bromodeoxyuridine; D006528:Carcinoma, Hepatocellular / Q000473:pathology*; D002453:Cell Cycle / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects*; D002855:Chromatography, Thin Layer; D004273:DNA, Neoplasm / Q000096:biosynthesis; D004305:Dose-Response Relationship, Drug; D005434:Flow Cytometry; D015870:Gene Expression / Q000187:drug effects; D016158:Genes, p53 / Q000187:drug effects*; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D029562:Magnoliaceae / Q000737:chemistry; D009569:Nitric Oxide / Q000502:physiology*; D019001:Nitric Oxide Synthase / Q000096:biosynthesis; D052247:Nitric Oxide Synthase Type II; D013055:Spectrophotometry, Infrared; D013056:Spectrophotometry, Ultraviolet; D014407:Tumor Cells, Cultured
chemical_list: D000963:Antimetabolites; D000972:Antineoplastic Agents, Phytogenic; D001060:Aporphines; D004273:DNA, Neoplasm; D009569:Nitric Oxide; C026980:liriodenine; C496319:NOS2 protein, human; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; D001973:Bromodeoxyuridine