Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0023418 (leukemia)
 93,477 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The mechanism of the antitumor action of 15-deoxyspergualin (DSG) was investigated. DSG inhibited spermidine synthase noncompetitively with putrescine, spermine synthase competitively with spermidine and polyamine oxidase in vitro. Induction of ornithine decarboxylase (ODC) activity observed after subculture of human leukemia cells was blocked by the addition of DSG to the culture medium. In DSG-treated leukemia cells, putrescine, spermidine and spermine levels were markedly depressed. The synthesis of protein was also greatly diminished in these polyamine-depleted leukemic cells, whereas the depressions of DNA and RNA syntheses were minimum. In in vivo experiments, DSG depressed polyamine levels in P388 leukemic ascites cells, and prolonged the survival times of mice bearing the leukemia cells. These results suggest that inhibition of polyamine and protein biosyntheses by DSG is substantially responsible for its antitumor action on the tumor cells.
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PMID:15-Deoxyspergualin, an antiproliferative agent for human and mouse leukemia cells shows inhibitory effects on the synthetic pathway of polyamines. 201 67

Methylglyoxal-bis(cyclopentylamidinohydrazone) (MGBCP) has been synthesized as a multienzyme inhibitor for the polyamine-synthesizing pathway. This drug inhibited S-adenosylmethionine decarboxylase (EC 4.1.1.50), spermine synthase and spermidine synthase activities, competitively with S-adenosylmethionine, spermidine, and putrescine, respectively. MGBCP inhibited the growth of human leukemia Molt 4B and K 562 cells at 10 to 100 microM concentrations. Spermidine and spermine levels were markedly depressed in these MGBCP-treated leukemic cells, and the synthesis of protein, but not of DNA or RNA, was significantly diminished. In in vivo experiments, MGBCP depleted spermidine and spermine in the P388 leukemic ascites cells, and prolonged the survival time of mice bearing P388 leukemia. The S-adenosylmethionine decarboxylase-stabilizing effect of MGBCP in mouse liver, Molt 4B and K 562 cells was much less than that of the parent inhibitor methylglyoxal-bis(guanylhydrazone). Induction of ornithine decarboxylase activity by MGBCP in the cultured leukemic cells was also much less than that by methylglyoxal-bis(guanylhydrazone).
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PMID:Antitumor effect of a new multienzyme inhibitor of polyamine synthetic pathway, methylglyoxal-bis(cyclopentylamidinohydrazone), against human and mouse leukemia cells. 270 49

Spermidine synthase from rat ventral prostate was inhibited by 2-mercaptoethylamine (MEA). Inhibition of spermidine synthase by MEA was competitive with respect to one of the substrates putrescine, but not competitive with respect to the other substrate decarboxylated S-adenosylmethionine. MEA markedly depressed spermidine and spermine contents in human erythroid leukemia K562 cells, suggesting that these changes resulted from the inhibitory effect of MEA on spermidine synthase in situ.
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PMID:2-Mercaptoethylamine, a competitive inhibitor of spermidine synthase in mammalian cells. 316 18

N-Chlorosulfonyl dicyclohexylamine (CSD) was synthesized as a potent inhibitor of spermidine synthase and analyzed for antiproliferative effects on leukemic cells. The compound specifically inhibited spermidine synthase in a competitive mode with the substrate putrescine (Ki, 1.8 X 10(-7) M). When human leukemia Molt4B cells were cultured in the presence of the inhibitor, the intracellular level of spermidine and the rate of cell proliferation were markedly depressed. In these polyamine depleted and growth retarded cells the synthesis of protein, but not of DNA or RNA, was found to be significantly diminished.
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PMID:Synthesis of N-chlorosulfonyl dicyclohexylamine as a potent inhibitor for spermidine synthase and its effects on human leukemia Molt4B cells. 380 Oct 21

The antitumor effect of dicyclohexylammonium sulfate (DCHA), a potent inhibitor of spermidine synthase, was tested on BDF1 mice inoculated i.p. with P388 leukemia (1 X 10(6) cells/mouse). DCHA prolonged the survival time of mice bearing P388 leukemia at the doses of 10-100 mg/kg administered daily for 6 days. The spleen weight increased by 30% at 7 days after tumor inoculation. DCHA treatment had no effect on the tumor-induced increase in splenic weight. The spermidine concentration of the ascites tumor cells and spleens of mice bearing the tumor was lowered by the treatment, while spermine concentration hardly changed. The depletion of spermidine in the ascites tumor cells and spleens might be a cause of the suppression of tumor growth.
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PMID:Antitumor effect of dicyclohexylammonium sulfate, a potent inhibitor of spermidine synthase against P388 leukemia. 711 28