Breast cancer and flavonoids - a role in prevention.
Breast cancer and flavonoids - a role in prevention.
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DOI：
10.2174/1381612811319340006
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发表时间：
2013-09
影响因子：
3.1
通讯作者：
H. Takemura;H. Sakakibara;Shunsuke Yamazaki;K. Shimoi
中科院分区：
文献类型：
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作者：
H. Takemura;H. Sakakibara;Shunsuke Yamazaki;K. Shimoi
内源性雌激素，如17β-雌二醇（E2），与乳腺癌的发展有关。雌激素发挥致癌作用的假定机制已被认为涉及雌激素代谢产物的氧化还原循环和随后的雌激素-DNA加合物形成以及雌激素诱导细胞生长的雌激素受体依赖性途径。前一种途径受I相酶的调节，主要是细胞色素P450（CYP）1A 1、1A 2和1B 1。其中，CYP 1B 1主要催化E2的C4位并形成致癌的4-羟基-E2（4-OHE 2），而CYP 1A 1和CYP 1A 2将E2转化为非致癌的2-羟基-E2。形成的4-OHE 2进一步氧化为半醌和醌，形成DNA加合物，导致诱变损伤。因此，CYP 1B 1高度表达，4-OHE 2主要在雌激素靶向肿瘤组织中检测到。此外，浸润和转移也参与了乳腺癌的发展。流行病学研究表明，黄酮类化合物的摄入量较高与乳腺癌风险之间存在负相关关系。黄酮类化合物广泛分布于植物界，最近被报道为对雌激素依赖性或非依赖性乳腺癌具有化学预防作用的候选化合物。在这篇综述中，我们提供了一个全面的概述乳腺癌和黄酮类化合物的化学预防，主要集中在ER介导的激素调节，雌激素代谢产物的氧化还原循环，和CYP 1B 1的选择性抑制。
Endogenous estrogens, such as 17β-estradiol (E2), are implicated in the development of breast cancer. The putative mechanisms by which estrogens exert the carcinogenic effects have been recognized to involve the redox cycling of estrogen metabolites and subsequent estrogen-DNA adduct formation as well as the estrogen receptor-dependent pathway of estrogen-induced cell growth. The former pathway is regulated by phase I enzymes, mainly cytochrome P450 (CYP) 1A1, 1A2, and 1B1. Among them, CYP1B1 predominantly catalyzes the C4-position of E2 and forms carcinogenic 4-hydroxy-E2 (4-OHE2), whereas CYP1A1 and CYP1A2 convert E2 to noncarcinogenic 2-hydroxy-E2. Formed 4-OHE2 is further oxidized to semiquinones and quinones, which form DNA adducts, leading to mutagenic lesions. Consequently, CYP1B1 is highly expressed, and 4-OHE2 is predominantly detected in estrogen target neoplastic tissues. Moreover, invasion and metastasis are also involved in the development of breast cancer. Epidemiological studies suggest an inverse association between a higher intake of flavonoids and breast cancer risk. Flavonoids, which are widely distributed in the plant kingdom, have been recently reported as candidate compounds that can exert chemopreventive effects in estrogen-dependent or independent breast cancer. In this review, we provide a comprehensive overview of breast cancer and chemoprevention by flavonoids, mainly focusing on ER-mediated hormonal regulation, redox cycling of estrogen metabolites, and selective inhibition of CYP1B1.