Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0019204 (hepatocellular carcinoma)
 71,386 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Activity and messenger RNA levels of spermidine/spermine N1-acetyltransferase, the rate-limiting enzyme of the polyamine interconversion pathway, were investigated in host liver and in Yoshida AH-130 ascites hepatoma cells as a function of tumor growth phases. Enzyme activity reached maximal values at day 10 in host liver (2.0-fold increase) and at days 10 and 14 in hepatoma cells (4.2- and 5.4-fold increases)--that is, when the cellular growth was nearly arrested. At day 10 the messenger RNA levels of spermidine/spermine N1-acetyltransferase were augmented concomitantly; they were about two and four times higher, respectively, in host liver and tumor cells than in control liver. The in vitro transcription rate seemed to be constant during hepatoma cell growth. Treatment of the animals with N1,N2-bis-(2,3-butadienyl)-1,4-butanediamine (MDL 72527), a specific inhibitor of polyamine oxidase, caused large accumulation of N1-acetylspermidine in hepatoma cells and in the ascitic fluid; the maximal values were reached at day 14. The levels of putrescine in inhibitor-treated rats decreased in hepatoma cells (day 5) and in ascitic fluid (days 5 and 14), whereas values of spermidine and spermine remained unchanged. The proposed role for spermidine/spermine N1-acetyltransferase-enhanced expression is to regulate the cellular polyamine pool by causing their excretion as acetylderivatives from tumor cells into the ascitic fluid, even if putrescine seems also to be excreted. Eventual repeat uptake of putrescine by hepatoma cells could contribute to the control of cellular polyamine levels.
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PMID:Expression of spermidine/spermine N1-acetyltransferase in growing Yoshida AH-130 hepatoma cells. 811

We screened genes responsive to transforming growth factor-beta (TGF-beta 1) protein in a human hepatoma cell line (Hep3B) using a PCR-mediated differential display technique, in order to investigate the mechanisms involved in TGF-beta-induced growth suppression. We found a gene that was down-regulated by TGF-beta 1 to be completely identical in an approx. 620 bp segment to the gene for the enzyme spermidine synthase, which mediates the conversion of putrescine into spermidine. Both spermidine synthase mRNA expression and its enzyme activity were decreased after TGF-beta 1 treatment of Hep3B cells. The inhibition of spermidine synthase gene expression by TGF-beta 1 protein was also observed in other hepatoma cell lines. The expression of genes for other biosynthetic enzymes in polyamine metabolism (ornithine decarboxylase and S-adenosylmethionine decarboxylase) was also inhibited to the same extent as for spermidine synthase, while the gene expression of spermidine/spermine N1-acetyltransferase, a catabolic enzyme, was relatively resistant to TGF-beta 1. Spermine levels in Hep3B cells were decreased by TGF-beta 1 treatment, although the levels of spermidine and putrescine were unchanged, probably due to compensation by remaining spermidine/spermine N1-acetyltransferase activity. Exogenously added spermidine or spermine, but not putrescine, partially antagonized the growth-inhibitor effects of TGF-beta 1 on Hep3B cells. Our data suggest that down-regulation of gene expression of the enzymes involved in polyamine metabolism, including spermidine synthase, may be associated with the mechanism of TGF-beta-induced growth suppression.
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PMID:Inhibition of spermidine synthase gene expression by transforming growth factor-beta 1 in hepatoma cells. 902 Aug 92

The objective of this study is to examine the effects of ANISpm, a novel polyamine naphthalimide conjugate, with acetylsalicylic acid against hepatocellular carcinoma in vivo and in vitro and elucidate its potential molecular mechanism. The proliferation inhibition was detected by MTT assay. Cell apoptosis, intracellular fluorescence intensity and mitochondrial membrane potential (MMP) were detected by high content screening (HCS) analysis. Polyamines content was analyzed by reverse-phase high performance liquid chromatography Protein expression levels were quantified by Western blotting assay. The combination treatment strongly inhibited cell proliferation, induced cell apoptosis in HepG2 cells and H22 hepatoma cells, which was mediated by enhanced ANISpm uptake via up-regulation of spermidine/spermine N1-acetyltransferase (SSAT) and depression of intracellular polyamine. Furthermore, this synergistic apoptosis was involved in mitochondria and death-receptor signal pathway. All these findings demonstrated that the combination treatment with acetylsalicylic acid and ANISpm resulted in synergistic antitumor effects on hepatoma cells. Thus, combination therapy with these agents may be useful as a potential template for the development of better chemotherapeutic strategy against hepatoma.
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PMID:[Acetylsalicylic acid strengthens the effects of ANISpm against hepatocellular carcinoma and its molecular mechanism]. 2212 73