mitoguazone and Liver-Neoplasms

Topics: Adenosylmethionine Decarboxylase; Animals; Breast; Cell Division; Chick Embryo; Female; Glucocorticoids; Half-Life; Liver Neoplasms; Male; Milk Proteins; Mitoguazone; Ornithine Decarboxylase; Ornithine Decarboxylase Inhibitors; Prostate; Putrescine; Pyridoxal Phosphate; Rabbits; Rats; RNA; Spermidine; Spermidine Synthase; Spermine

The antitumor effects of a polyamine biosynthetic pathway inhibitor methylglyoxal bis(cyclopentylamidinohydrazone) (MGBCP) on the human hepatocellular carcinoma SK-HEP-1 cell line have been investigated. The growth of these cultured hepatocellular carcinoma cells was inhibited by MGBCP in a dose-dependent manner. Spermidine and spermine levels were dose-dependently depressed, and morphological changes due to programmed cell death (apoptosis) were observed in these MGBCP-treated hepatocellular carcinoma cells. These results suggest that in addition to reducing the growth rates, MGBCP can induce apoptotic cell death in this human hepatocellular carcinoma cell line.

Topics: Antineoplastic Agents; Apoptosis; Carcinoma, Hepatocellular; Cell Division; DNA Fragmentation; Dose-Response Relationship, Drug; Humans; Liver Neoplasms; Mitoguazone; Polyamines; Tumor Cells, Cultured

1. By 1h after administration of ethionine to the female rat the appearance of newly synthesized 18SrRNA in the cytoplasm is completely inhibited. This is not caused by inhibition of RNA synthesis, for the synthesis of the large ribosomal precursor RNA (45S) and of tRNA continues. Cleavage of 45S RNA to 32S RNA also occurs, but there was no evidence for the accumulation of mature or immature rRNA in the nucleus. 2. The effect of ethionine on the maturation of rRNA was not mimicked by an inhibitor of protein synthesis (cycloheximide) or an inhibitor of polyamine synthesis [methylglyoxal bis(guanylhydrazone)]. 3. Unlike the ethionine-induced inhibition of protein synthesis, this effect was not prevented by concurrent administration of inosine. A similar effect could be induced in HeLa cells by incubation for 1h in a medium lacking methionine. The ATP concentration in these cells was normal. From these two observations it was concluded that the effect of etionine on rRNA maturation is not caused by an ethionine-induced lack of ATP. It is suggested that ethionine, by lowering the hepatic concentration of S-adenosylmethionine, prevents methylation of the ribosomal precursor. The methylation is essential for the correct maturation of the molecule; without methylation complete degradation occurs.

Topics: Adenosine Triphosphate; Animals; Cycloheximide; Ethionine; Female; HeLa Cells; Inosine; Liver; Liver Neoplasms; Methionine; Methylation; Mitoguazone; Rats; RNA; RNA, Ribosomal; RNA, Transfer; S-Adenosylmethionine