Stable ornithine decarboxylase in a rat hepatoma cell line selected for resistance to α-difluoromethylornithine

Mitchell, John L.A.; Hoff, Jane A.; Bareyal-Leyser, Aviva

doi:10.1016/0003-9861(91)90600-n

Cited by 21 publications

(30 citation statements)

References 48 publications

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“…These could include amplification of ODC in some tissues, as has been reported in cell-culture models 88 , or increased uptake of polyamines from bacterial flora in the intestinal lumen. Both of these mechanisms could overcome the inhibitory effects of DFMO.…”

Section: Use Of Dfmo In Combination Withmentioning

confidence: 87%

Polyamines and cancer: old molecules, new understanding

2004

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| The amino-acid-derived polyamines have long been associated with cell growth and cancer, and specific oncogenes and tumour-suppressor genes regulate polyamine metabolism. Inhibition of polyamine synthesis has proven to be generally ineffective as an anticancer strategy in clinical trials, but it is a potent cancer chemoprevention strategy in preclinical studies. Clinical trials, with well-defined goals, are now underway to evaluate the chemopreventive efficacy of inhibitors of polyamine synthesis in a range of tissues. UREA CYCLEThe key metabolic pathway in mammals for eliminating cellular breakdown products containing nitrogen. NATURE REVIEWS | CANCER VOLUME 4 | OCTOBER 2004 | 7 8 1

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Section: Use Of Dfmo In Combination Withmentioning

confidence: 87%

Polyamines and cancer: old molecules, new understanding

2004

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“…Work in our laboratory and others has shown that excess putrescine accumulation by uptake from the medium and\or by synthesis as the result of overproduction of ODC is toxic in mammalian cells in itro as well [14][15][16]. Selection of hepatoma tissue culture (HTC) cells in α-difluoromethylornithine (DFMO), an inhibitor of ODC, has produced a cell line, DH23A\b, that produces aberrantly high levels of very stable ODC [23] and overaccumulates putrescine in the absence of DFMO [16]. Overaccumulation of putrescine in these cells results in cell death [14,16] ; however, the mechanism by which putrescine causes cell death is not known.…”

Section: Introductionmentioning

confidence: 99%

“…These studies were designed to elucidate the mechanism by which putrescine may cause cell death. [23]. HTC and DH23A cells were grown as described [16].…”

Section: Introductionmentioning

confidence: 99%

Excess putrescine accumulation inhibits the formation of modified eukaryotic initiation factor 5A (eIF-5A) and induces apoptosis

Tome

Fišer

Payne

et al. 1997

Biochemical Journal

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DH23A cells, an α-difluoromethylornithine-resistant variant of the parental hepatoma tissue culture cells, express high levels of stable ornithine decarboxylase. Aberrantly high expression of ornithine decarboxylase results in a large accumulation of endogenous putrescine and increased apoptosis in DH23A cells when α-difluoromethylornithine is removed from the culture. Treatment of DH23A cells with exogenous putrescine in the presence of α-difluoromethylornithine mimics the effect of drug removal, suggesting that putrescine is a causative agent or trigger of apoptosis. Accumulation of excess intracellular putrescine inhibits the formation of hypusine in vivo, a reaction that proceeds by the transfer of the butylamine moiety of spermidine to a lysine residue in eukaryotic initiation factor 5A (eIF-5A). Treatment of DH23A cells with diaminoheptane, a competitive inhibitor of the post-translational modification of eIF-5A, causes both the suppression of eIF-5A modification in vivo and induction of apoptosis. These data support the hypothesis that rapid degradation of ornithine decarboxylase is a protective mechanism to avoid cell toxicity from putrescine accumulation. Further, these data suggest that suppression of modified eIF-5A formation is one mechanism by which cells may be induced to undergo apoptosis.

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“…Antibody preparations Rabbit antibody to pure ODC was prepared as previously described [22], and the specificity was enhanced for immunoblot experiments by affinity purification using pure ODC bound to Affi-Gel 10 (Bio-Rad). Affinity-purified polyclonal rabbit antibody specific for antizyme was prepared by using an antizyme fusion protein expressed in bacteria.…”

Section: Introductionmentioning

confidence: 99%

“…This fusion protein was purified by affinity to a 2 ml column of GSH-agarose (Sigma) followed by gradient elution from a Mono-Q (Pharmacia) ion-exchange column. The pure fusion protein was used to prepare polyclonal antibody as described previously [22], and immunoreactive rabbit serum was further purified by affinity to fusion protein bound to Affi-Gel 10 (Bio-Rad).…”

Section: Introductionmentioning

confidence: 99%

Feedback repression of polyamine transport is mediated by antizyme in mammalian tissue-culture cells

Mitchell

Judd

Bareyal-Leyser

et al. 1994

Biochemical Journal

208

156

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Antizyme, a spermidine-induced protein that binds and stimulates ornithine decarboxylase degradation, is now shown also to mediate the rapid feedback inhibition of polyamine uptake into mammalian cells. Using a cell line (HZ7) transfected with truncated antizyme cDNA, and mutant ornithine decarboxylase cell lines, we demonstrate that this newly discovered action of antizyme is distinct from its role in modulating polyamine biosynthesis.

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Stable ornithine decarboxylase in a rat hepatoma cell line selected for resistance to α-difluoromethylornithine

Cited by 21 publications

References 48 publications

Polyamines and cancer: old molecules, new understanding

Polyamines and cancer: old molecules, new understanding

Excess putrescine accumulation inhibits the formation of modified eukaryotic initiation factor 5A (eIF-5A) and induces apoptosis

Feedback repression of polyamine transport is mediated by antizyme in mammalian tissue-culture cells

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