Nutrition & Cancer, 2011, 63(8):1279-86.

Inhibitory Effects of Combination of Lycopene and Genistein on 7,12- Dimethyl Benz(a)anthracene-Induced Breast Cancer in Rats

Kazim Sahin, et al

Department of Animal Nutrition, Faculty of Veterinary Science, Firat University, Elazig, Turkey; et al

Breast cancer is one of the most common cancers in women. Carotenoids and soy isoflavones have been postulated to have breast cancer preventive effects. We investigated the potential preventive effects of lycopene and genistein, alone and in combination, on breast cancer development in female Wistar rats treated with 7,12-dimethylbenz[a]anthracene (DMBA), a carcinogen known to induce breast tumors. Mammary carcinogenesis was initiated by a single, oral gavage of DMBA (80 mg/kg body weight) at 55 days of animal age. Fifty female Wistar rats were divided into 5 experimental groups having 10 animals per group: Group 1 (normal control), Group 2 (DMBA control), Group 3 (DMBA + lycopene), Group 4 (DMBA + genistein), and Group 5 (DMBA + lycopene and genistein). Rats were fed either lycopene (20 mg /kg bw) or genistein (2 mg /kg bw) by oral gavage (3 times per week) starting 2 wk prior to DMBA injection. Treatment was continued for 20 wk. Rats treated with DMBA developed mammary tumors with 100% tumor incidence during the 20-wk study. Inhibition of mammary cancer incidence by lycopene (70%), genistein (60%) and their combination (40%) was observed. Tumor weight decreased by 48%, 61%, and 67%, and mean tumor volume decreased by 18%, 35%, and 65% with lycopene, genistein, and lycopene + genistein, respectively (P < 0.01 for the combination). The proportions of adenocarcinoma masses decreased with lycopene and genistein combination (P < 0.05). Administration of lycopene and genistein combination suppressed breast cancer development and was associated with a decrease in MDA, 8-isoprostane, and 8-OhdG levels and with an increase in serum lycopene and genistein levels. Animals administered DMBA developed breast cancer, which was associated with increased expression of Bcl-2 and decreased expression of Bax, caspase 3, and caspase 9 in mammary tissues. Administration of genistein and lycopene in combination was more effective in inhibiting DMBA-induced breast tumors and modulating the expression of apoptosis associated proteins than the administration of each agent alone. Our results suggest that lycopene and genistein are potent antioxidants and, when given in combination, offer maximum protection against DMBA-induced mammary carcinogenesis.

美国《营养与癌症》，2011年11月

在大鼠中番茄红素联合三羟异黄酮对 7,12-二甲基苯 (a) 蒽诱发的乳腺癌的抑制效应

卡齐姆 沙欣等

土耳其幼发拉底河大学兽医科学院动物营养系等

乳腺癌是女性最常见的癌症之一。据推测类胡萝卜素和大豆异黄酮具有预防乳房癌的效果。我们探究了用 7，12-二甲基苯并 [a] 蒽 (DMBA)这种已知可引起乳腺肿瘤的一种致癌物质处理的患有乳腺癌的雌性大鼠中番茄红素和金雀异黄素潜在的预防作用，单独和联合。首先对55 天年龄的动物单一、 口腔灌注DMBA （80 mg/kg体重）来诱发乳腺癌。50只雌性大鼠被分为 5 个实验组，每组 10只︰1组（普通对照），2组（DMBA 对照）、3组（DMBA + 番茄红素）、4 组（DMBA + 金雀异黄素） 和5组（DMBA + 番茄红素和金雀异黄素）。在开始 给DMBA 注射前2 周给大鼠口服喂食番茄红素 (20 mg /kg bw) 或金雀异黄素 (2 mg /kg bw)（每周 3 次）。对大鼠的治疗持续了20 个星期。在20个星期的研究期内用DMBA处理的老鼠表现出 100%的乳腺癌发病率。检测由番茄红素 （70%）、 金雀异黄素 （60%） 和它们的组合 （40%）抑制的乳腺癌发病率。对于番茄红素、 染料木黄酮，和番茄红素 + 金雀异黄素的治疗方法，肿瘤重量分别下降了 48%、 61%和 67%，平均肿瘤体积分别减小了 18%、 35%和 65% (P < 0.01)。肿瘤块的比例在番茄红素和金雀异黄素组合的作用下减小 (P < 0.05)。番茄红素和金雀异黄素组合给药抑制了乳腺癌的发展并且与血清番茄红素和金雀异黄素水平增加以及MDA、 8-异前列烷 和 8-羟基脱氧鸟苷 浓度降低有关。动物被给药 DMBA后诱发的乳腺癌，与在乳腺组织中Bcl-2 的表达增加， Bax、 半胱氨酸蛋白酶 3 和半胱氨酸蛋白酶 9的表达减少有关。染料木素和番茄红素的联合给药在抑制 DMBA 诱导的乳腺肿瘤和调节理细胞凋亡相关蛋白的表达方面比单独试剂更有效。我们的结果表明，番茄红素和染料木黄酮是有效的抗氧化剂，并且当联合使用时，可以为DMBA 诱导的乳腺肿瘤提供最大程度的防护作用。