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用于癌症预防和治疗的膳食因子的分子靶点。

Molecular targets of dietary agents for prevention and therapy of cancer.

作者信息

Aggarwal Bharat B, Shishodia Shishir

机构信息

Cytokine Research Laboratory, Department of Experimental Therapeutics, The University of Texas M.D. Anderson Cancer Center, Box 143, 1515 Holcombe Boulevard, Houston, TX 77030, USA.

出版信息

Biochem Pharmacol. 2006 May 14;71(10):1397-421. doi: 10.1016/j.bcp.2006.02.009. Epub 2006 Feb 23.

Abstract

While fruits and vegetables are recommended for prevention of cancer and other diseases, their active ingredients (at the molecular level) and their mechanisms of action less well understood. Extensive research during the last half century has identified various molecular targets that can potentially be used not only for the prevention of cancer but also for treatment. However, lack of success with targeted monotherapy resulting from bypass mechanisms has forced researchers to employ either combination therapy or agents that interfere with multiple cell-signaling pathways. In this review, we present evidence that numerous agents identified from fruits and vegetables can interfere with several cell-signaling pathways. The agents include curcumin (turmeric), resveratrol (red grapes, peanuts and berries), genistein (soybean), diallyl sulfide (allium), S-allyl cysteine (allium), allicin (garlic), lycopene (tomato), capsaicin (red chilli), diosgenin (fenugreek), 6-gingerol (ginger), ellagic acid (pomegranate), ursolic acid (apple, pears, prunes), silymarin (milk thistle), anethol (anise, camphor, and fennel), catechins (green tea), eugenol (cloves), indole-3-carbinol (cruciferous vegetables), limonene (citrus fruits), beta carotene (carrots), and dietary fiber. For instance, the cell-signaling pathways inhibited by curcumin alone include NF-kappaB, AP-1, STAT3, Akt, Bcl-2, Bcl-X(L), caspases, PARP, IKK, EGFR, HER2, JNK, MAPK, COX2, and 5-LOX. The active principle identified in fruit and vegetables and the molecular targets modulated may be the basis for how these dietary agents not only prevent but also treat cancer and other diseases. This work reaffirms what Hippocrates said 25 centuries ago, let food be thy medicine and medicine be thy food.

摘要

虽然推荐食用水果和蔬菜来预防癌症和其他疾病,但其活性成分(在分子水平上)及其作用机制尚不太清楚。在过去的半个世纪里,广泛的研究已经确定了各种分子靶点,这些靶点不仅可用于预防癌症,还可用于治疗。然而,由于旁路机制导致靶向单一疗法失败,迫使研究人员采用联合疗法或干扰多种细胞信号通路的药物。在这篇综述中,我们提供证据表明,从水果和蔬菜中鉴定出的许多药物可以干扰多种细胞信号通路。这些药物包括姜黄素(姜黄)、白藜芦醇(红葡萄、花生和浆果)、染料木黄酮(大豆)、二烯丙基硫醚(葱属植物)、S-烯丙基半胱氨酸(葱属植物)、大蒜素(大蒜)、番茄红素(番茄)、辣椒素(红辣椒)、薯蓣皂苷元(胡芦巴)、6-姜酚(生姜)、鞣花酸(石榴)、熊果酸(苹果、梨、李子)、水飞蓟宾(水飞蓟)、茴香脑(茴芹、樟脑和茴香)、儿茶素(绿茶)、丁香酚(丁香)、吲哚-3-甲醇(十字花科蔬菜)、柠檬烯(柑橘类水果)、β-胡萝卜素(胡萝卜)和膳食纤维。例如,仅姜黄素就能抑制的细胞信号通路包括核因子κB、活化蛋白-1、信号转导和转录激活因子3、蛋白激酶B、B细胞淋巴瘤/白血病-2、Bcl-XL、半胱天冬酶、聚(ADP-核糖)聚合酶、IκB激酶、表皮生长因子受体、人表皮生长因子受体2、应激活化蛋白激酶、丝裂原活化蛋白激酶、环氧化酶-2和5-脂氧合酶。在水果和蔬菜中鉴定出的活性成分以及所调节的分子靶点可能是这些膳食药物不仅能预防而且能治疗癌症和其他疾病的基础。这项工作再次肯定了25个世纪前希波克拉底所说的话:让食物成为你的药物,让药物成为你的食物。

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