Role of resveratrol in prevention and therapy of cancer: preclinical and clinical studies.
Role of resveratrol in prevention and therapy of cancer: preclinical and clinical studies.
复制标题
DOI：
--
复制
发表时间：
2004-09
影响因子：
2
通讯作者：
B. Aggarwal;A. Bhardwaj;Rishi S Aggarwal;N. Seeram;S. Shishodia;Y. Takada
中科院分区：
文献类型：
--
作者：
B. Aggarwal;A. Bhardwaj;Rishi S Aggarwal;N. Seeram;S. Shishodia;Y. Takada
白藜芦醇，反式-3，5，4 '-三羟基芪，1940年首次作为白色藜芦（Veratrum grandiflorum O.）但后来在各种植物中发现了这种物质，包括葡萄、浆果和花生。除了心脏保护作用，白藜芦醇还表现出抗癌特性，如其抑制多种肿瘤细胞增殖的能力所表明的，所述肿瘤细胞包括淋巴和骨髓癌;多发性骨髓瘤;乳腺癌、前列腺癌、胃癌、结肠癌、胰腺癌和甲状腺癌;黑色素瘤;头颈部鳞状细胞癌;卵巢癌;和宫颈癌。白藜芦醇的生长抑制作用是通过细胞周期阻滞; p21 Cip 1/WAF 1、p53和Bax的上调;生存素、细胞周期蛋白D1、细胞周期蛋白E、Bcl-2、Bcl-xL和cIAPs的下调;以及半胱天冬酶的激活来介导的。已显示白藜芦醇抑制几种转录因子的活化，包括NF-κ B、AP-1和Egr-1;抑制蛋白激酶，包括IkappaB α激酶、JNK、MAPK、Akt、PKC、PKD和酪蛋白激酶II;并下调基因产物，如考克斯-2、5-LOX、VEGF、IL-1、IL-6、IL-8、AR和PSA。这些活动说明了这种芪对血管生成的抑制作用。白藜芦醇还显示出增强细胞因子（例如，TRAIL）、化疗剂和γ-辐射。药代动力学研究表明，白藜芦醇的靶器官是肝脏和肾脏，在吸收后浓缩，主要转化为硫酸化形式和葡糖苷酸结合物。在体内，白藜芦醇在不同阶段阻断致癌的多步骤过程：它通过抑制芳烃诱导的CYP 1A 1表达和活性来阻断致癌物活化，并抑制肿瘤的发生、促进和进展。除了化学预防作用，白藜芦醇似乎对癌症有治疗作用。有限的人类数据表明，白藜芦醇是非常安全的。目前，具有改善的生物利用度的白藜芦醇的结构类似物正被追求作为潜在的癌症治疗剂。
Resveratrol, trans-3,5,4'-trihydroxystilbene, was first isolated in 1940 as a constituent of the roots of white hellebore (Veratrum grandiflorum O. Loes), but has since been found in various plants, including grapes, berries and peanuts. Besides cardioprotective effects, resveratrol exhibits anticancer properties, as suggested by its ability to suppress proliferation of a wide variety of tumor cells, including lymphoid and myeloid cancers; multiple myeloma; cancers of the breast, prostate, stomach, colon, pancreas, and thyroid; melanoma; head and neck squamous cell carcinoma; ovarian carcinoma; and cervical carcinoma. The growth-inhibitory effects of resveratrol are mediated through cell-cycle arrest; upregulation of p21Cip1/WAF1, p53 and Bax; down-regulation of survivin, cyclin D1, cyclin E, Bcl-2, Bcl-xL and clAPs; and activation of caspases. Resveratrol has been shown to suppress the activation of several transcription factors, including NF-kappaB, AP-1 and Egr-1; to inhibit protein kinases including IkappaBalpha kinase, JNK, MAPK, Akt, PKC, PKD and casein kinase II; and to down-regulate products of genes such as COX-2, 5-LOX, VEGF, IL-1, IL-6, IL-8, AR and PSA. These activities account for the suppression of angiogenesis by this stilbene. Resveratrol also has been shown to potentiate the apoptotic effects of cytokines (e.g., TRAIL), chemotherapeutic agents and gamma-radiation. Phamacokinetic studies revealed that the target organs of resveratrol are liver and kidney, where it is concentrated after absorption and is mainly converted to a sulfated form and a glucuronide conjugate. In vivo, resveratrol blocks the multistep process of carcinogenesis at various stages: it blocks carcinogen activation by inhibiting aryl hydrocarbon-induced CYP1A1 expression and activity, and suppresses tumor initiation, promotion and progression. Besides chemopreventive effects, resveratrol appears to exhibit therapeutic effects against cancer. Limited data in humans have revealed that resveratrol is pharmacologically quite safe. Currently, structural analogues of resveratrol with improved bioavailability are being pursued as potential therapeutic agents for cancer.