Methionine Restriction Inhibits Colon Carcinogenesis

  title={Methionine Restriction Inhibits Colon Carcinogenesis},
  author={Despina Komninou and Yvonne Leutzinger and Bandaru S. Reddy and John P. Richie Jr.},
  journal={Nutrition and Cancer},
  pages={202 - 208}
Previously, we demonstrated that life-long methionine restriction (MR) in rats increases life span and inhibits aging-related disease processes. [] Key Method Six-week-old male F344 rats were placed on essential amino acid-defined diets containing either 0.86% Met (control diet) or 0.17% Met (MR diet) and 1 wk later were given AOM (15 mg/kg/wk, s.c.) for 2 consecutive wk. Ten weeks after the final AOM treatment, ACF formation was markedly reduced in rats fed the MR diet with ACF containing > or = 4 crypts…
Methionine restriction delays aging-related urogenital diseases in male Fischer 344 rats
Results suggest that MR may lead to metabolic and cellular changes providing protection against age-related diseases, as indicated by the absence of renal pathology and urinary albumin levels.
Methionine-restricted diet inhibits growth of MCF10AT1-derived mammary tumors by increasing cell cycle inhibitors in athymic nude mice
The application of MR in a clinical setting may provide a delay in the progression of cancer, which would provide more time for conventional cancer therapies to be effective.
Methionine restriction inhibits chemically-induced malignant transformation in the BALB/c 3T3 cell transformation assay.
Azoxymethane-induced colon carcinogenesis in mice occurs independently of de novo thymidylate synthesis capacity.
Enrichment of SHMT1 in the cytoplasm, as observed in Shmt1(tg+) mice, protects against AOM-mediated carcinogenesis independent of its role in nuclear de novo dTMP biosynthesis.
Methionine restriction affects oxidative stress and glutathione-related redox pathways in the rat
Findings indicate that oxidative stress is reduced by MR feeding in rats, but this effect cannot be explained by changes in the activity of antioxidant enzymes.
Dietary methionine restriction improves colon tight junction barrier function and alters claudin expression pattern.
Reduction in dietary intake of methionine results in improved epithelial barrier function by inducing altered TJ protein composition in rat gastrointestinal tissue, suggesting improved barrier function relative to rats on control diet.
Methyl Donor Deficiency Blocks Colorectal Cancer Development by Affecting Key Metabolic Pathways
Findings provide clues to the molecular changes underlying MDD-mediated tumor protection and identify regulatable metabolic pathways that may provide new targets for colorectal cancer prevention and treatment.
Methionine restriction beyond life‐span extension
Research on dietary methionine restriction and its involvement in metabolism, cancer, and epigenetics is summarized.


Methionine restriction increases blood glutathione and longevity in F344 rats
The results suggest that dramatic adaptations in sulfur amino acid metabolism occur as a result of chronic Met restriction, leading to increases in blood GSH levels and conservation of tissue GSH during aging.
Dietary polyamines promote the growth of azoxymethane-induced aberrant crypt foci in rat colon.
It was demonstrated that dietary polyamines are able to enhance the growth of AOM-induced aberrant crypt foci in rat colon and reversed the DFMO-caused inhibition of ACF growth, probably by compensating for the DF MO-reduced endogenous polyamine synthesis.
Effects of caloric restriction and dietary fat on epithelial cell proliferation in rat colon.
Caloric restriction is effective in favorably modulating CCP, an intermediate biomarker of colon cancer risk; a high fat ad libitum diet, which increased tumor yield, does not increase distal colon proliferation; dietary fat intake alters proliferation in a manner differing from that induced by changing dietary caloric intake.
Nutritional control of aging
Chemoprevention of colon carcinogenesis by concurrent administration of piroxicam, a nonsteroidal antiinflammatory drug with D,L-alpha-difluoromethylornithine, an ornithine decarboxylase inhibitor, in diet.
A dose-dependent inhibition in colon adenocarcinoma incidence with increasing levels of piroxicam or DFMO was suggested and linear regression method suggested a stronger inhibitory effect than did those given individually.
Long-term effects of caloric restriction initiated at different ages on DNA polymerases in rat brain
Regional distribution of carcinogen-induced colonic neoplasia in the rat.
This AOM model of colon tumor formation approximates human colon cancer distribution and is an appropriate model for rodent chemopreventive studies.
Effect of long-term depletion of plasma methionine on the growth and survival of human brain tumor xenografts in athymic mice.
The data strongly support the use of methionine-depleting regimens for tumor treatments and show that when this procedure is applied to athymic mice bearing human medulloblastoma (Daoy) tumors subcutaneously, tumor growth is inhibited.
Decreased rat rhabdomyosarcoma pulmonary metastases in response to a low methionine diet.
The rationale of the experiments described herein was to decrease the in vivo growth of malignant tumors by reducing the exogenous methionine available in diets fed to Wistar AG rats bearing the highly metastatic rhabdomyosarcoma, RMS-J1.