Banerjee Sanjeev, Bueso-Ramos Carlos, Aggarwal Bharat B
Cytokine Research Laboratory, Department of Bioimmunotherapy, The University of Texas M. D. Anderson Cancer Center, Houston, Texas 77030, USA.
Cancer Res. 2002 Sep 1;62(17):4945-54.
We have reported recently that resveratrol (trans-3,4',5-trihydroxystilbene), a polyphenolic phytoalexin found in grapes, fruits, and root extracts of the weed Polygonum cuspidatum, is a potent inhibitor of nuclear factor (NF)-kappaB activation. Because NF-kappaB suppression has been linked with chemoprevention, this prompted us to investigate the chemopreventive potential of resveratrol by testing it against mammary carcinogenesis induced by 7,12-dimethylbenz(a)anthracene (DMBA) in female Sprague Dawley rats. Dietary administration of resveratrol (10 ppm) had no effect on body weight gain and tumor volume but produced striking reductions in the incidence (45%; P < 0.05), multiplicity (55%; P < 0.001), and extended latency period of tumor development relative to DMBA-treated animals. Histopathological analysis of the tumors revealed that DMBA induced ductal carcinomas and focal microinvasion in situ (7 of 7), whereas treatment with resveratrol suppressed DMBA-induced ductal carcinoma. Immunohistochemistry and Western blot analysis revealed that resveratrol suppressed the DMBA-induced cyclooxygenase-2 and matrix metalloprotease-9 expression in the breast tumor. Gel shift analysis showed suppression of DMBA-induced NF-kappaB activation by resveratrol. Treatment of human breast cancer MCF-7 cells with resveratrol also suppressed the NF-kappaB activation and inhibited proliferation at S-G(2)-M phase. Overall, our results suggest that resveratrol suppresses DMBA-induced mammary carcinogenesis, which correlates with down-regulation of NF-kappaB, cyclooxygenase-2, and matrix metalloprotease-9 expression.
我们最近报道，白藜芦醇（反式-3,4',5-三羟基芪）是一种在葡萄、水果以及杂草虎杖的根提取物中发现的多酚类植物抗毒素，它是核因子（NF）-κB激活的有效抑制剂。由于NF-κB抑制与化学预防有关，这促使我们通过在雌性斯普拉格-道利大鼠中测试白藜芦醇对7,12-二甲基苯并(a)蒽（DMBA）诱导的乳腺癌发生的作用，来研究其化学预防潜力。饮食给予白藜芦醇（10 ppm）对体重增加和肿瘤体积没有影响，但相对于DMBA处理的动物，肿瘤发生率（45%；P < 0.05）、多发性（55%；P < 0.001）和肿瘤发生的潜伏期显著降低。肿瘤的组织病理学分析显示，DMBA诱导导管癌和原位局灶微浸润（7/7），而白藜芦醇处理抑制了DMBA诱导的导管癌。免疫组织化学和蛋白质印迹分析显示，白藜芦醇抑制乳腺肿瘤中DMBA诱导的环氧化酶-2和基质金属蛋白酶-9表达。凝胶迁移分析表明白藜芦醇抑制DMBA诱导的NF-κB激活。用白藜芦醇处理人乳腺癌MCF-7细胞也抑制了NF-κB激活并抑制了S-G(2)-M期的增殖。总体而言，我们的结果表明白藜芦醇抑制DMBA诱导的乳腺癌发生，这与NF-κB、环氧化酶-2和基质金属蛋白酶-9表达的下调相关。
