Chemoprevention by dietary agents/supplements has emerged as a novel approach to control various malignancies, including colorectal cancer (CRC). This study assessed dietary grape seed extract (GSE) effectiveness in preventing azoxymethane (AOM)-induced aberrant crypt foci (ACF) formation and associated mechanisms in Fischer 344 rats. Six-week-old rats were injected with AOM, and fed control diet or the one supplemented with 0.25% or 0.5% (w/w) GSE in pre- and post-AOM or only post-AOM experimental protocols.
We have recently shown that American ginseng (AG) prevents and treats mouse colitis. Because both mice and humans with chronic colitis have a high colon cancer risk, we tested the hypothesis that AG can be used to prevent colitis-driven colon cancer. Using the azoxymethane (AOM)/dextran sulfate sodium (DSS) mouse model of ulcerative colitis, we show that AG can suppress colon cancer associated with colitis. To explore the molecular mechanisms of the anticancer effects of AG, we also carried out antibody array experiments on colon cells isolated at a precancerous stage.
Myeloid Translocation Gene, Related-1 (MTGR1) CBFA2T2 is a member of the Myeloid Translocation Gene (MTG) family of transcriptional corepressors. The remaining two family members, MTG8 (RUNX1T1) and MTG16 (CBFA2T3) are identified as targets of chromosomal translocations in acute myeloid leukemia (AML). Mtgr1(-/-) mice have defects in intestinal lineage allocation and wound healing. Moreover, these mice show signs of impaired intestinal stem cell function. Based on these phenotypes, we hypothesized that MTGR1 may influence tumorigenesis arising in an inflammatory background.
Chronic inflammation is an underlying risk factor for colon cancer. Tumor necrosis factor alpha (TNF-α) plays a critical role in the development of inflammation-induced colon cancer in a mouse model. S-adenosylmethionine (SAMe) and its metabolite methylthioadenosine (MTA) can inhibit lipopolysaccharide-induced TNF-α expression in macrophages. The aim of this work was to examine whether SAMe and MTA are effective in preventing inflammation-induced colon cancer and if so identify signaling pathways affected.
The inverse correlation between levels of dietary calcium and colorectal cancer (CRC) incidence has been extensively investigated. However, the impact of supplemental calcium on cancer therapy remains unknown. We used four models of CRC, Caco-2 and HCT116 human cancer cell lines and Apc (Min/+) and azoxymethane carcinogen-induced mouse models, to investigate the impact of a western-style diet low in calcium (0.05%) vs. a similar diet but supplemented with calcium (5%) on therapeutic targeting of the epidermal growth factor receptor (EGFR).
Molecule-targeted therapies are being widely developed and deployed, but they are frequently less effective in clinical trials than predicted based upon preclinical studies. Frequently, only a single model or genetic background is utilized using diets that are not relevant to that consumed by most cancer patients, which may contribute to the lack of predictability of many preclinical therapeutic studies. Inhibition of epidermal growth factor receptor (EGFR) in colorectal cancer was used to investigate potential causes for low predictive values of many preclinical studies.
Colorectal cancer (CRC) is the second leading cause of cancer-associated deaths, suggesting that additional strategies are needed to prevent/control this malignancy. As CRC growth and progression involve a large window (10-15 years), chemopreventive intervention could be a practical/translational strategy. Azoxymethane (AOM)-induced colon tumorigenesis in mice resembles human CRC in terms of progression of ACF to polyps, adenoma, and carcinomas and associated molecular mechanisms.
In cancer, genetic mutations have long been considered to be the only driver of neoplasia. However, there is increasing evidence that epigenetic alterations could also play a major role in carcinogenesis and cancer. A number of experimental and epidemiologic studies have shown that many classes of dietary phytochemicals possess cancer-preventive and epigenetic-modifying properties. The report by Derry and colleagues in this issue of the journal shows that grape seed extract (GSE) prevents azoxymethane (AOM)-induced colon colitis via epigenetic microRNA (miRNA) regulation.
Selenium (Se) is an essential micronutrient that exerts its functions via selenoproteins. Little is known about the role of Se in inflammatory bowel disease (IBD). Epidemiological studies have inversely correlated nutritional Se status with IBD severity and colon cancer risk. Moreover, molecular studies have revealed that Se deficiency activates WNT signaling, a pathway essential to intestinal stem cell programs and pivotal to injury recovery processes in IBD that is also activated in inflammatory neoplastic transformation.
Yakugaku Zasshi: Journal of the Pharmaceutical Society of Japan
Daphne genkwa (Thymelaeaceae) has been used as a folk medicine in China. We investigated the effects of D. genkwa and Jyu-So-To on various pharmacologic models in mice including the azoxymethane (AOM)-induced colonic aberrant crypt focus formation assay, ornithine decarboxylase (ODC) activity assay, and two types of mouse ear swelling model. Administration of 236.3 ppm of Jyu-So-To in drinking water significantly suppressed AOM-induced colonic aberrant crypt focus formation (p < 0.05), with an inhibitory ratio of 46.7%. The effects of several extracts with organic solvents of D.