Aging alters folate homeostasis and DNA damage response in colon.

The risk for developing colorectal cancer increases exponentially with age. We demonstrate that spontaneous loss of folate in the colon results in DNA damage accumulation and aberrant DNA damage responses that may contribute to the increased genomic instability and cancer risk in colon. We find greater than 2-fold changes in the expression of folate-absorption and folate retention genes within the colonocyte, demonstrating that with age the colon is able to induce expression of appropriate genes in response to limiting folate status.

Suppression of breast xenograft growth and progression in nude mice: implications for the use of orally administered sphingolipids as chemopreventive agents against breast cancer.

Sphingolipids are lipid messengers involved in the regulation of many different cellular processes. Sphingolipid enzymes and bioactive metabolites have been targets of in vitro and in vivo efforts to suppress cancer growth, progression and metastasis of various cancer types. Dietary sphingomyelin effectively suppressed colon cancer in several rodent models without causing toxic side effects.

Regulation of beta-catenin and connexin-43 expression: targets for sphingolipids in colon cancer prevention.

Sphingolipid metabolites are generated throughout the intestinal tract after hydrolysis of orally administered complex sphingolipids and significantly suppress colon cancer in carcinogen-treated CF1 mice. In the present study, the mechanisms of tumor suppression by dietary sphingolipids were investigated. Changes in select genes that are critical in early stages of colon cancer were analyzed in the colonic mucosa of dimethylhydrazine-treated CF1 mice fed AIN76A diet with or without 0.