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Nutrition and Disease

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^1–3,

⁴ Toxicology Research Division, Bureau of Chemical Safety, Food Directorate, Health Canada, K1A 0L2 Ottawa, Ontario and ⁵ Department of Biological Sciences, University of Windsor, N9B 3P4 Windsor, Ontario

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.

^* To whom correspondence should be addressed. E-mail: jayadev_raju{at}hc-sc.gc.ca.

Manuscript received 3 September 2008. Initial review completed 6 October 2008. Revision accepted 10 December 2008.

Published online 13 January 2009.