Polyamines in gastrointestinal cancer

Saydjari, Rami; Townsend, Courtney M.; Barranco, S. C.; Thompson, James C.

doi:10.1007/bf01537125

Cited by 19 publications

(10 citation statements)

References 53 publications

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“… 113 The biosynthesis of polyamines in mammalian cells begins with the decarboxylation of ornithine to form the diamine putrescine. This is the first and rate‐limiting step in the polyamine biosynthetic pathway, and is governed by the enzyme ornithine decarboxylase (ODC) 114 …”

Section: α‐Difluoromethylornithinementioning

confidence: 99%

Chemoprevention of colorectal cancer

Courtney

Melville

Leicester

2003

Aliment Pharmacol Ther

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SUMMARYColorectal cancer is a disease with a high mortality at present, due to the late stage at which many cases present. Attention is therefore focusing on preventative strategies for colorectal cancer given that polyps appear to be identifiable and treatable precursor lesions of this disease. Endoscopic polypectomy has been shown to reduce the incidence of colorectal cancer and there is a good case for endoscopic screening of the general population. However, this will require a large amount of manpower and resources and its success will also depend on the overall compliance of the population.Epidemiological studies have shown that individuals reporting a regular intake of aspirin and other nonsteroidal anti-inflammatory drugs have a reduced risk of developing colorectal polyps and cancer. Similarly, a number of natural substances, such as calcium and folate, when supplemented regularly in the diet, have also been linked to a possible decreased incidence of colorectal cancer. This has led to the concept of using such agents to reduce the number of cases of colorectal cancer. In this article, we review the current evidence for the use of these and other agents for the chemoprevention of colorectal cancer, together with theories as to their possible mechanisms of action.

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Section: α‐Difluoromethylornithinementioning

confidence: 99%

Chemoprevention of colorectal cancer

Courtney

Melville

Leicester

2003

Aliment Pharmacol Ther

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“…Since ornithine is then not converted to putrescine, DFMO inhibits polyamine biosynthesis. Investigators in our laboratory have recently reported that DFMO inhibits the growth of hamster pancreatic ductal adenocarcinoma (H2T) [6] and mouse colon cancer (MC-26) [7] in vitro. Other investigators have demonstrated similar effects by polyamine inhibitors in several other types of neoplasms, both in vitro and in vivo [5,[8][9][10].…”

Section: Introductionmentioning

confidence: 99%

Cyclosporine and α-difluoromethylornithine exhibit differential effects on colon and pancreatic cancer in vitro

Saydjari¹,

Townsend²,

Barranco³

et al. 1987

Invest New Drugs

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alpha-Difluoromethylornithine (DFMO) is a known irreversible inhibitor of ornithine decarboxylase (ODC), the rate-limiting enzyme in polyamine biosynthesis. Cyclosporine (CsA) has been reported to inhibit ODC activity in vitro. In the present study, we compared the effects of DFMO and CsA on growth, survival, and polyamine levels in mouse colon cancer (MC-26) and hamster pancreatic cancer (H2T) cells in vitro. The growth and survival of MC-26 and H2T cells were inhibited by both DFMO and CsA. However, H2T cells were observed to be significantly more sensitive than MC-26 cells to both CsA and DFMO. The inhibitory effects of CsA were blocked by the addition of the polyamine, putrescine, in both MC-26 and H2T cells. Polyamine levels were altered significantly in both MC-26 and H2T cells treated with CsA and DFMO. However, the profile of these alterations differed between MC-26 and H2T cell lines. Putrescine and spermidine levels in MC-26 cells were more sensitive to DFMO inhibition than were H2T cells. Spermine levels were consistently elevated in MC-26 cells exposed to CsA or DFMO, while the level of spermine in H2T cells decreased significantly in response to the same drugs. These results suggest that CsA and DFMO exhibit different effects on colon and pancreatic cancer growth in vitro. In addition, the differences in the sensitivity of pancreatic and colon cancer to CsA and DFMO indicate potentially important differences in polyamine metabolism between the two cell lines.

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“…There has been particular interest in polyamine metabolism in malignant cells [40], in part reflecting its potential as a chemotherapeutic target since deprivation of polyamines, by inhibition of polyamine synthesis with ornithine analogues such as a-difluoromethylornithine, restrains growth. ODC activity has also been investigated as a means of discriminating premalignant from malignant conditions, especially colorectal neoplasia with elevated levels in neoplastic tissue (reviewed in [41]).…”

Section: Other Markers Of the Cell Cyclementioning

confidence: 99%