Mediterranean diet, olive oil and cancer.
Mediterranean diet, olive oil and cancer.
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DOI：
10.1007/s12094-006-0090-0
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发表时间：
2006-01-01
期刊：
影响因子：
--
通讯作者：
Menendez, Javier A
中科院分区：
文献类型：
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作者：
Colomer, Ramon;Menendez, Javier A
橄榄油是“地中海饮食”的一个组成部分，越来越多的证据表明，它可能在降低几种癌症的风险方面具有潜在的作用。然而，橄榄油预防癌症的作用机制尚不清楚。我们最近假设，关于橄榄油抗癌作用的一种新的分子解释可能与其单不饱和脂肪酸（MUFA）油酸（OA; 18：1 n-9）特异性调节癌症相关癌基因的能力有关。支持我们的假设，外源性补充培养的乳腺癌细胞与生理浓度的OA被发现抑制HER 2（Her-2/neu，erbB-2），一个充分表征的癌基因的过度表达发挥了关键作用的病因，进展和化疗和内分泌治疗约20%的乳腺癌。还发现OA治疗可协同增强曲妥珠单抗的疗效，曲妥珠单抗是一种与Her 2编码的p185（HER 2）癌蛋白的胞外域（ECD）具有高亲和力结合的人源化单克隆抗体。此外，OA暴露显著减少了HER 2的ECD的蛋白水解裂解，因此，其活化状态是决定Her 2过表达乳腺癌的侵袭性行为和对曲妥珠单抗的反应的关键分子事件。我们最近的研究结果进一步揭示，OA暴露可能通过上调Ets蛋白PEA 3（一种特异性阻断HER 2启动子活性的DNA结合蛋白）在乳腺癌、卵巢癌和胃癌细胞系中的表达，在转录水平上抑制HER 2。OA的这种抗HER 2特性提供了一种以前未被认识的分子机制，橄榄油可以通过这种机制调节癌细胞的恶性行为。从临床的角度来看，它可以提供一种有效的手段，影响Her-2/neu过度表达的人类癌症的预后不良的结果。事实上，OA诱导的HER 2癌基因转录抑制可能代表了一种新的基因组解释，将“地中海饮食”，橄榄油和癌症联系起来，因为它似乎在各种类型的Her-2/neu相关癌中同样起作用。
Olive oil is an integral ingredient of the "Mediterranean diet" and accumulating evidence suggests that it may have a potential role in lowering the risk of several types of cancers. The mechanisms by which the cancer-preventing effects of olive oil can be performed, however, are not known. We recently hypothesized that a novel molecular explanation concerning the anti-cancer actions of olive oil may relate to the ability of its monounsaturated fatty acid (MUFA) oleic acid (OA; 18:1n-9) to specifically regulate cancer-related oncogenes. Supporting our hypothesis, exogenous supplementation of cultured breast cancer cells with physiological concentrations of OA was found to suppress the overexpression of HER2 (Her-2/neu, erbB-2), a well-characterized oncogene playing a key role in the etiology, progression and response to chemotherapy and endocrine therapy in approximately 20% of breast carcinomas. OA treatment was also found to synergistically enhance the efficacy of trastuzumab, a humanized monoclonal antibody binding with high affinity to the ectodomain (ECD) of the Her2-coded p185(HER2) oncoprotein. Moreover, OA exposure significantly diminished the proteolytic cleavage of the ECD of HER2 and, consequently, its activation status, a crucial molecular event that determines both the aggressive behavior and the response to trastuzumab of Her2-overexpressing breast carcinomas. Our most recent findings further reveal that OA exposure may suppresses HER2 at the transcriptional level by up-regulating the expression of the Ets protein PEA3 -a DNA-binding protein that specifically blocks HER2 promoter activity- in breast, ovarian and stomach cancer cell lines. This anti-HER2 property of OA offers a previously unrecognized molecular mechanism by which olive oil may regulate the malignant behavior of cancer cells. From a clinical perspective, it could provide an effective means of influencing the outcome of Her-2/neu-overexpressing human carcinomas with poor prognosis. Indeed, OA-induced transcriptional repression of HER2 oncogene may represent a novel genomic explanation linking "Mediterranean diet", olive oil and cancer as it seems to equally operate in various types of Her-2/neu-related carcinomas.