Chemoprevention of precursors to colon cancer by dehydroepiandrosterone (DHEA).
Although dehydroepiandrosterone (DHEA) is recognized as one of the major adrenal androgens, its precise physiological role in the human endocrine system remains to be elucidated. In particular, the effect of DHEA on carcinogenesis has not been fully characterized. We undertook this study to determine whether DHEA has a chemopreventative effect on the precursors of colon cancer in a murine model of azoxymethane (AOM)-induced aberrant crypt foci (ACF). The number of ACF was significantly decreased in mice treated with 0.4% (p < 0.001) and 0.8% DHEA (p < 0.001), but there were no significant differences between DHEA-treated and control mice in terms of the ACF size, 3-catenin expression or level of dysplasia. This is the first study of colon cancer carcinogenesis demonstrating that DHEA treatment can decrease the number of ACF without apparently modifying their malignant potential. These data strongly suggest that DHEA might be a potential chemopreventative agent against human colon cancer.
Osawa
Emi
E
The Third Department of Internal Medicine, Yokohama City University School of Medicine, Yokohama, Kanagawa, Japan.
Nakajima
Atsushi
A
Yoshida
Sachiko
S
Omura
Masao
M
Nagase
Hajime
H
Ueno
Norio
N
Wada
Koichiro
K
Matsuhashi
Nobuyuki
N
Ochiai
Masako
M
Nakagama
Hitoshi
H
Sekihara
Hisahiko
H
D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D000818:Animals; D001397:Azoxymethane / Q000633:toxicity; D002273:Carcinogens / Q000633:toxicity; D018890:Chemoprevention; D003110:Colonic Neoplasms / Q000139:chemically induced / Q000473:pathology / Q000517:prevention & control*; D003598:Cytoskeletal Proteins / Q000378:metabolism; D003687:Dehydroepiandrosterone / Q000494:pharmacology*; D004032:Diet; D005260:Female; D007124:Immunoenzyme Techniques; D007413:Intestinal Mucosa / Q000187:drug effects; D051379:Mice; D008807:Mice, Inbred BALB C; D011230:Precancerous Conditions / Q000139:chemically induced / Q000473:pathology / Q000517:prevention & control*; D015534:Trans-Activators / Q000378:metabolism; D051176:beta Catenin
D000276:Adjuvants, Immunologic; C495267:CTNNB1 protein, mouse; D002273:Carcinogens; D003598:Cytoskeletal Proteins; D015534:Trans-Activators; D051176:beta Catenin; D003687:Dehydroepiandrosterone; D001397:Azoxymethane