We found that CRC cells overexpress ODC and treatment with DFMO decreases cancer hallmarks including enhanced cell proliferation and apoptosis resistance.
The G316 > A functional variant in the ODC gene is unlikely to make much impact on reducing CRC risk regardless of the reduction in risk found for the recurrence of colorectal adenoma.
We had blocked the polyamine synthesis pathway using the adenoviral-mediated antisense ODC in some cancer cells such as prostate cancers and colorectal cancers.
Interestingly, before the intervention, ornithine decarboxylase 1 promoter methylation was lower in the colonic mucosa of the adenoma polyp patients when compared with healthy control subjects, which may explain the increased ornithine decarboxylase 1 activity in CRC reported in the literature.
Genotype-specific survival differences were observed among colorectal cancer cases: compared with cases with the ODC1 GG genotype (hazards ratio, 1; reference) the adjusted colorectal cancer-specific survival hazards ratio was 2.02 (95% confidence interval, 1.17-3.50) for ODC1 GA/AA cases (P = 0.012).
In animal experiments, HT29/ODC and LoVo/ODC cell xenografts demonstrated growth suppression compared to parental or control colorectal cancer cell xenografts.
APC and APC-dependent genes, such as c-Myc and ODC, may be useful as genetic markers of risk and as targets for chemoprevention and therapy for colorectal cancer.
Our aim was to evaluate the ornithine decarboxylase activity and polyamine levels in samples of colorectal carcinoma and uninvolved surrounding mucosa from 86 patients (52 men and 34 women) showing different patterns of K-ras/p53 mutations.
Mutation of the Kirsten-ras (Ki-ras) proto-oncogene occurs frequently in colorectal cancers. alpha-Difluoromethylornithine (DFMO), an irreversible inhibitor of the polyamine biosynthetic enzyme, ornithine decarboxylase (ODC), inhibits Ki-ras transformation and colon tumorigenesis in carcinogen-treated animal models by mechanisms yet to be elucidated.
Moreover, we found that ODC activity was significantly higher in neoplastic tissue than in surrounding normal mucosa in polypoid type colorectal cancer.
Because mutation of ODC in primary human hepatocellular carcinoma has been reported, we examined whether the genetic alterations, such as mutations or structural alterations of the gene, also account for the alteration of ODC activity in human colorectal cancer.
We examined somatic mutations of ODC cDNA by RT-PCR-SSCP analysis and mRNA expressions by RT-PCR in 50 colorectal cancer tissues to investigate the involvement of ODC gene alterations in colorectal cancers.
The expression of ODC and c-myc mRNA in biopsy specimens obtained from both tumor tissue and the corresponding normal tissue was examined by the reverse transcriptase polymerase chain reaction method in 40 cases of colorectal carcinoma.
We measured sigmoid and rectal mucosal ODC activity levels in 45 healthy, disease-free subjects with strong family histories of colorectal cancer before and after 2 months, during which daily dietary supplementation with calcium carbonate (to provide 600 mg calcium base) was taken.