Vitamin K3 inhibits growth of human hepatoma HepG2 cells by decreasing activities of both p34cdc2 kinase and phosphatase.
Synthetic vitamin K3 is known to exhibit in vitro and in vivo antitumor activity against rodent and human cancer cells. To determine vitamin K3's effect on the cell cycle, we treated both synchronized and asynchronized human hepatoma HepG2 cells with 100 microM vitamin K3 for 1 h and followed cells to recover for various times, then monitored cell cycle progression by flow cytometry and by phosphorylation status of p34cdc2 kinase. Vitamin K3 induced a delay at the S/G2 phase of the cell cycle. This was accompanied by constant hyperphosphorylation status and decreased activity of p34cdc2 kinase. Protein-tyrosine phosphatase activity also decreased 2- to 3-fold after vitamin K3 treatment. Our results suggest that vitamin K3 inhibits the growth of HepG2 cells via a cell cycle progression delay and altered phosphorylation patterns and activities of both p34cdc2 kinase and protein-tyrosine phosphatase.
Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan, Republic of China.
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D016203:CDC2 Protein Kinase / Q000378:metabolism*; D006528:Carcinoma, Hepatocellular / Q000473:pathology*; D002453:Cell Cycle / Q000187:drug effects*; D006131:Growth Inhibitors; D006801:Humans; D066298:In Vitro Techniques; D008113:Liver Neoplasms / Q000473:pathology; D010749:Phosphoprotein Phosphatases / Q000378:metabolism*; D010766:Phosphorylation; D014407:Tumor Cells, Cultured; D014812:Vitamin K / Q000494:pharmacology*
D006131:Growth Inhibitors; D014812:Vitamin K; D016203:CDC2 Protein Kinase; D010749:Phosphoprotein Phosphatases