Journal
CANCER PREVENTION RESEARCH
Volume 2, Issue 1, Pages 52-59Publisher
AMER ASSOC CANCER RESEARCH
DOI: 10.1158/1940-6207.CAPR-08-0140
Keywords
-
Categories
Funding
- USPHS National Cancer Institute [N01-CN-53300, R01-CA-94962]
- NATIONAL CANCER INSTITUTE [R01CA094962] Funding Source: NIH RePORTER
Ask authors/readers for more resources
Raloxifene, selective estrogen receptor (ER) modulator, is not fully explored in colorectal cancer. In the present study we, (a) investigated the effect of raloxifene on ER-positive colon cancer HCT-116 cell growth, (b) assessed the relevance of ER-beta in colon tumorigenesis, and (c) assessed the chemopreventive efficacy of raloxifene against azoxymethane (AOM)-induced colon carcinogenesis using aberrant crypt foci (ACF) as surrogate end point marker. HCT-116 cells treated with raloxifene showed a significant decrease in cell growth associated with a decrease in ER-beta expression levels. AOM-induced colon adenocarcinoma showed significant up-regulation of ER-beta expression at both the protein and mRNA levels compared with normal mucosa, suggesting that ER-beta is positively associated with colon cancer. An assay using five different dietary dose levels (0.31, 0.62, 1.25, 2.5, or 5 ppm) of raloxifene for 6 weeks in male F344 rats found the maximum tolerated dose to be 5 ppm. To evaluate inhibitory properties of raloxifene on colonic ACF, 7-week-old rats were fed experimental diets containing 0, 0.625, 1.25, and 2.5 ppm of raloxifene. After 1 week, rats received s.c. injections of AOM, 15 mg/kg body weight, once weekly for 2 weeks. Rats continued to receive respective experimental diets and sacrificed 8 weeks after the last AOM treatment. Raloxifene given in the diet significantly inhibited AOM-induced total colonic ACF (31-40%; P < 0.001-0.0005) and multicrypt (four or more) aberrant foci (23-50%; P < 0.05-0.005) in F344 rats. Our findings suggest that ER-beta acts as a colon tumor promoter and raloxifene as an antagonist to ER-beta, providing protection against colon carcinogenesis.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available