Liriodenine inhibits the proliferation of human hepatoma cell lines by blocking cell cycle progression and nitric oxide-mediated activation of p53 expression.
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.
Hsieh
Tian-Jye
TJ
Basic Medical Science Education Center, Fooyin University, Ta-Liao, Kaohsiung Hsien 831, Taiwan, ROC.
Liu
Tsan-Zon
TZ
Chern
Chi-Liang
CL
Tsao
Der-An
DA
Lu
Fung-Jou
FJ
Syu
Yu-Hua
YH
Hsieh
Pei-Ying
PY
Hu
Han-Shu
HS
Chang
Ting-Ting
TT
Chen
Ching-Hsein
CH
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
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