Open AccessSoy Isoflavones Modulate Azoxymethane-Induced Rat Colon Carcinogenesis Exposed Pre- and Postnatally and Inhibit Growth of DLD-1 Human Colon Adenocarcinoma Cells by Increasing the Expression of Estrogen Receptor-β
Author(s) -
Jayadev Raju,
A Bielecki,
Donald Caldwell,
E. Lok,
Marnie Taylor,
Kamla Kapal,
Ivan Curran,
Gerard M. Cooke,
Ranjana P. Bird,
Rekha Mehta
Publication year - 2009
Publication title -
the journal of nutrition/the journal of nutrition
Language(s) - English
Resource type - Journals
eISSN - 1541-6100
pISSN - 0022-3166
DOI - 10.3945/jn.108.099200
Subject(s) - azoxymethane , isoflavones , endocrinology , estrogen receptor , medicine , aberrant crypt foci , phytoestrogens , colorectal cancer , estrogen , adenocarcinoma , chemistry , cancer , breast cancer , colonic disease
We studied the effects of lifetime exposure to dietary soy isoflavones in an azoxymethane (AOM)-induced rat colon cancer model. Male pups born to Sprague-Dawley rats exposed (including during pregnancy and lactation) to soy isoflavones at either no (0 mg = control), low (40 mg), or high (1000 mg) doses/kg diet were weaned and continued receiving their respective parental diets until the end of the study. Weaned rats received 2 subcutaneous injections (15 mg/kg body weight) of AOM 1 wk apart. After 26 wk, rats were killed and the coordinates of colon aberrant crypt foci (ACF) and tumors were determined. Expression of estrogen receptor (ER)-beta was assessed in rat colon tumors and in DLD-1 human colon adenocarcinoma cells exposed to soy isoflavones. Compared with the control, soy isoflavones did not affect incidences or multiplicities of colon ACF or tumors. Low-dose soy isoflavones decreased tumor burden and size compared with the control (P < 0.05). Expression of ERbeta increased in colon tumors of soy isoflavone-treated groups compared with the control. Soy isoflavones dose-dependently arrested the growth of DLD-1 cells and at subcytotoxic levels increased the expression of ERbeta. Our results suggest that pre- and postnatal exposure to dietary soy isoflavones suppresses the growth of colon tumors in male rats. The overexpression of ERbeta in both rat colon tumors and DLD-1 cells caused by soy isoflavones suggests that ERbeta is a critical mediator in mitigating its cancer-preventive effects.