Soy 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

• Published in: The Journal of nutrition Vol. 139; no. 3; pp. 474 - 481
• Main Authors: Raju, Jayadev, Bielecki, Agnieszka, Caldwell, Donald, Lok, Eric, Taylor, Marnie, Kapal, Kamla, Curran, Ivan, Cooke, Gerard M, Bird, Ranjana P, Mehta, Rekha
• Format: Journal Article
• Language: English
• Published: United States American Society for Nutrition 01.03.2009
• Subjects: adenocarcinoma; Adenocarcinoma - drug therapy; Adenocarcinoma - prevention & control; animal models; Animals; Animals, Newborn; azoxymethane; Azoxymethane - toxicity; bone density; Carcinogens - toxicity; Cell Line, Tumor; Colonic Neoplasms - chemically induced; Colonic Neoplasms - drug therapy; Colonic Neoplasms - prevention & control; colorectal neoplasms; Diet; dietary exposure; Estrogen Receptor beta - genetics; Estrogen Receptor beta - metabolism; estrogen receptor-alpha; estrogenic properties; Female; fetus; Gene Expression Regulation, Neoplastic - drug effects; Glycine max - chemistry; human cell lines; Humans; isoflavones; Isoflavones - chemistry; Isoflavones - pharmacology; Male; postnatal development; Pregnancy; prenatal development; Prenatal Exposure Delayed Effects; Random Allocation; Rats; Rats, Sprague-Dawley
• ISSN: 0022-3166; 1541-6100
• DOI: 10.3945/jn.108.099200

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)-β 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 ERβ 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 ERβ. Our results suggest that pre- and postnatal exposure to dietary soy isoflavones suppresses the growth of colon tumors in male rats. The overexpression of ERβ in both rat colon tumors and DLD-1 cells caused by soy isoflavones suggests that ERβ is a critical mediator in mitigating its cancer-preventive effects.