Antitumor Activities Of Gibberellin Derivatives G And J And Their Effects On Cell Cycle

OBJECTIVE: To investigate the antitumor activity of compound G and J, two kinds of gibberellin derivatives and their effect on cell cycle progression. METHODS: The inhibitory effects of G and J on tumor growth were observed by the models of implanted sarcoma 180 (S180) and hepatoma 22 (H22) in mice. The antitumor effects of compound G and J on hepatoma G2 bearing in nude mice were also evaluated. By using flow cytometry and trypan blue staining assay, the effects of G and J on cell cycle progression and cytotoxicity in human cancer cell lines were studied. Furthermore, the acute-toxicity of G and J was observed by means of peros (po) in ICR mice. RESULTS: G and J at the dose of 0.1,0.5,2.5 mg/kg administrated by oral route inhibited significantly the growth of S180 and H22 bearing in mice, respectively. It also showed that G (0.1 mg/kg) and J (2.5 mg/kg) inhibited the growth of hepatoma G2 bearing in nude mice significantly. G and J inhibited the proliferation of A549 and HL60 cell at G1 phase in a time depending manner in a certain extent, and they suppressed the growth of tumor cells significantly. The acute maximal tolerance dose toxicity testing showed that the medial lethal dose (LD50) of G was under 5 mg/kg. CONCLUSION: Compound G and J had significant antitumor effects in vivo, and they were capable of arresting the cell cycle at G1 phase, which may be one of the mechanisms of antitumor action.