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-beta.
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.
Raju
Jayadev
J
Toxicology Research Division, Bureau of Chemical Safety, Food Directorate, Health Canada, K1A 0L2 Ottawa, Ontario. jayadev_raju@hc-sc.gc.ca
Bielecki
Agnieszka
A
Caldwell
Donald
D
Lok
Eric
E
Taylor
Marnie
M
Kapal
Kamla
K
Curran
Ivan
I
Cooke
Gerard M
GM
Bird
Ranjana P
RP
Mehta
Rekha
R
D000230:Adenocarcinoma / Q000188:drug therapy / Q000517:prevention & control*; D000818:Animals; D000831:Animals, Newborn; D001397:Azoxymethane / Q000633:toxicity; D002273:Carcinogens / Q000633:toxicity; D045744:Cell Line, Tumor; D003110:Colonic Neoplasms / Q000139:chemically induced / Q000188:drug therapy / Q000517:prevention & control*; D004032:Diet; D047629:Estrogen Receptor beta / Q000235:genetics / Q000378:metabolism*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D007529:Isoflavones / Q000737:chemistry / Q000494:pharmacology*; D008297:Male; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D013025:Glycine max / Q000737:chemistry*
D002273:Carcinogens; D047629:Estrogen Receptor beta; D007529:Isoflavones; D001397:Azoxymethane