mitoguazone and methylglyoxal-bis(butylamidinohydrazone)

The antitumor effect of a polyamine biosynthetic pathway inhibitor methylglyloxal bis(butylamidinohydrazone) (MGBB) on human malignant melanoma (HMG) cells and its combination effect with cisplatin were investigated. The growth of cultured HMG cells was inhibited in a dose dependent manner by either MGBB or cisplatin; complete inhibition of cell proliferation was attained with 5 micrograms/ml of MGBB or 50 micrograms/ml of cisplatin. Pretreatment of HMG cells with MGBB diminished the antitumor action of cisplatin. The cultured HMG cells were inoculated in nude mice and aliquots of the resulting solid tumors (HMG tumor) were transplanted. The growth of transplanted HMG tumors in mice was inhibited markedly by cisplatin (3.8 mg/kg) and moderately by MGBB (10 or 20 mg/kg). The in vivo antitumor effect of cisplatin was also reduced by combined treatment with MGBB.

Topics: Animals; Antineoplastic Agents; Cell Division; Cisplatin; Female; Humans; Melanoma, Experimental; Mice; Mice, Inbred BALB C; Mice, Nude; Mitoguazone; Neoplasm Transplantation; Transplantation, Heterologous; Tumor Cells, Cultured

Metabolic and antiproliferative effects of methylglyoxal bis(butylamidinohydrazone) (MGBB) and methylglyoxal bis(cyclopentylamidinohydrazone) (MGBCP), inhibitors for polyamine biosynthetic pathway, on Escherichia coli, Shigella sonnei, Aeromonas sobria, Aeromonas hydrophila and Vibrio cholerae were investigated. MGBB at the concentration of 100 mumol/l depleted intracellular putrescine and spermidine concentrations of E. coli to 25 and 20% of the controls, respectively, while MGBCP depressed their concentrations to 38 and 24%, respectively. In these polyamine-depleted E. coli cells the syntheses of RNA, DNA and protein decreased to 13, 54 and 29% of the control, respectively, with MGBB and to 23, 71 and 55%, respectively, with MGBCP. The minimum inhibitory concentrations (MIC) of MGBB for the growth of A. sobria, E. coli, A. hydrophila, V. cholerae and Sh. sonnei were estimated to be 50, 160, 240, 285 and 320 mumol/l, respectively, whereas those of MGBCP were slightly higher for respective bacteria.

Topics: Bacteria; Bacterial Proteins; Biogenic Polyamines; Escherichia coli; Mitoguazone

Methylglyoxal bis(butylamidinohydrazone) (MGBB) inhibited S-adenosylmethionine decarboxylase (SAMDC) activity competitively with S-adenosylmethionine (SAM) showing the Ki value of 1.8 X 10(-5) M. MGBB showed less SAMDC-stabilizing effect in rat liver in vivo than did methylglyoxal bis-(guanylhydrazone) (MGBG). MGBB inhibited the growth of human erythroid leukemia K 562 cells. Putrescine, spermidine and spermine concentrations in MGBB-treated cells were depressed to 56%, 58% and 88% of the values of control cells, respectively. [35S]Methionine incorporation into trichloroacetic acid-insoluble fraction was decreased in the inhibitor-treated cells.

Topics: Adenosylmethionine Decarboxylase; Animals; Carboxy-Lyases; Cell Line; Humans; Leukemia, Erythroblastic, Acute; Liver; Male; Mitoguazone; Polyamines; Rats; Rats, Inbred Strains

Topics: Adenosylmethionine Decarboxylase; Animals; Carboxy-Lyases; Kinetics; Mitoguazone; Ornithine Decarboxylase Inhibitors; Rats; Spermidine Synthase; Transferases

The activities of ornithine decarboxylase (ODC) and spermidine/spermine N1-acetyltransferase (SAT) were increased by the addition of S-adenosylmethionine decarboxylase (AdoMetDC) inhibitor methylglyoxal bis(guanylhydrazone) (MGBG) in cultured human erythroid leukemia K 562 cells. ODC activity began to increase 4 hr after the addition of the drug and attained a maximum at 12 hr. The increase of SAT activity lagged behind that of ODC activity. The increases of both ODC and SAT activities produced by MGBG were blocked by treatment with cycloheximide, suggesting that the increase of enzyme activity resulted from the synthesis of new enzyme proteins. The putrescine content in cells treated with MGBG increased markedly, whereas the levels of spermidine and spermine were depressed lower. On the other hand, methylglyoxal bis(butylamidinohydrazone) (MGBB), a derivative of MGBG inhibiting AdoMetDC effectively, did not induce ODC or SAT activities.

Topics: Acetyltransferases; Adenosylmethionine Decarboxylase; Carboxy-Lyases; Cell Line; Enzyme Induction; Humans; Mitoguazone; Ornithine Decarboxylase; Polyamines