白藜芦醇与癌的化学预防

白藜芦醇,又名3,5,4′-三羟基反苯二烯,是一种存在于葡萄及其他一些天然产物中的多酚类化合物.白藜芦醇在癌症的始发、促进及发展阶段均表现出显著的抑制作用,因此它被认为是极有希望成为癌症的化学预防药物.本文就白藜芦醇在癌的化学预防方面的作用,包括抗氧化、抗突变、抗促癌、调控细胞周期、诱导凋亡和激素调节等作用及其机制做一综述.     

白藜芦醇对人结肠癌SW480瘤株作用的研究

目的研究白藜芦醇对人结肠癌细胞株SW480生长和细胞周期的影响,并探讨其作用机制。方法采用光镜及电子显微镜观察用药前后细胞形态结构的改变;采用四唑盐(MTT)比色法检测细胞增殖,采用流式细胞术测定细胞周期。结果白藜芦醇呈时间和剂量依赖性抑制人结肠癌细胞株SW480的生长并诱导凋亡,IC50为80μmol/L;白藜芦醇使SW480处于S期细胞增多。结论白藜芦醇能有效的抑制人结肠癌细胞株SW480的生长并诱导其凋亡;白藜芦醇对结肠癌可能是一种有效的化学治疗和化学预防药物。     

白藜芦醇用于预防和治疗结直肠癌的研究进展

近年来研究显示,白藜芦醇具有抗氧化、抗炎的特性,能够调节细胞内糖和神经酰胺的代谢,激活转录激活因子3和过氧化物酶体增殖物激活受体γ等抑癌因子,又可下调鼠类肉瘤病毒癌基因的表达,抑制癌细胞上皮间质转化的发生等,使得白藜芦醇在预防和治疗结直肠癌方面发挥重要作用.另外,白藜芦醇在联合治疗中显示出广阔的应用前景.     

白藜芦醇的抗肿瘤效应机制

白藜芦醇是一种天然多酚类化合物,具有多种生物学作用,包括神经保护作用、心血管保护作用、抗炎及抗肿瘤作用等.近年来白藜芦醇抗肿瘤作用日益受到关注,其抗肿瘤机制可能是预防肿瘤的发生、延缓肿瘤的发展、促进肿瘤细胞凋亡及抑制肿瘤细胞的侵袭等.     

白藜芦醇抗癌的生物学机制研究进展

白藜芦醇是一种天然存在的植物多酚类抗毒素，具有广泛的生物学活性，如抗氧化、抗炎、免疫调节以及神经保护等。白藜芦醇抗肿瘤活性备受关注，且得到广泛研究，但作用机制尚不明确。白藜芦醇作为低聚物，分子结构特性使其作为癌症预防剂和治疗剂有广阔前景。本文主要从白藜芦醇通过抑制细胞色素酶、作为化疗制剂、抑制COX-2、调控细胞周期、诱导癌细胞凋亡、抑制肿瘤细胞血管生成、调控细胞因子NF-κB、诱导细胞自噬、抑制癌细胞转移方面进行综述。     

白藜芦醇抗肿瘤血管生成机制

白藜芦醇是一种多酚类化合物，能通过多种途径抑制肿瘤的起始、促进和发展3个阶段，具有抑制血管生成的作用。现就白藜芦醇抑制肿瘤新生血管的生成和生长的机制作一综述。     

白藜芦醇对癌的化学预防作用

背景与目的：白藜芦醇广泛存在于药食两用植物中,其开发利用已得到越来越多的关注。本研究旨在依据癌发生、发展的多阶段理论,选用经典的动物模型,从多个靶点探讨白藜芦醇对癌的化学预防作用。方法：采用抗Ames法、抗微核法检测白藜芦醇抗突变作用。巴豆油诱发的小鼠耳肿胀和小鼠表皮组织中鸟氨酸脱羧酶的活性来判断其抗促癌作用。通过检测二甲基苯蒽／巴豆油诱发的小鼠皮肤二阶段乳头状瘤模型全面观察其对肿瘤发生的抑制作用。结果：白藜芦醇可以明显减少致癌剂诱发的鼠伤寒沙门氏菌TA100回复突变菌落数,每皿用量100μg对甲基磺酸甲酯作用的抑制率达42．2％,每皿200μg对苯并芘作用的抑制率达91．8％。提前灌喂白藜芦醇可以显著对抗环磷酰胺诱发的小鼠骨髓嗜多染红细胞微核增加,并呈现较好的剂量依赖关系。将白藜芦醇以每日30mg／kg剂量灌喂6天,能有效减轻致炎剂引起的小鼠耳部急性炎性反应。以每日180mg／kg剂量给药3天,对巴豆油激发的小鼠表皮组织鸟氨酸脱羧酶活性增高抑制率达69．3％。应用白藜芦醇可以推迟二甲基苯蒽／巴豆油诱发的小鼠皮肤乳头状瘤发生时间,降低肿瘤发生率,减少平均荷瘤数。结论：白藜芦醇在癌发生的突变、促癌及演进各阶段均可发挥积极的对抗作用。作为癌化学预防剂,具有较好的开发应用前景。     

白藜芦醇对胃癌细胞HGC27细胞周期的影响

目的：研究白藜芦醇对胃癌细胞株HGC27细胞细胞周期的影响。方法：不同浓度的白藜芦醇作用于HGC27细胞,用流式细胞术分析细胞周期。结果：白藜芦醇作用后,HGC27细胞的增殖速度减缓,DNA合成减少。白藜芦醇在较低浓度时即可诱导G0／G1阻滞。结论：白藜芦醇可诱导胃癌细胞发生G0／G1阻滞,S期减少。     

白藜芦醇抑制MCF-7乳腺癌细胞增殖的机制研究

研究白藜芦醇对MCF-7乳腺癌细胞抑制效应及其作用机制。方法:以人MCF-7乳腺癌细胞株为研究对象,利用MTT方法研究白藜芦醇抑制MCF-7乳腺癌细胞的生物学效应;观察在ERK1/2抑制剂PD98059预处理情况下,白藜芦醇抑制MCF-7乳腺癌细胞增殖效应的改变;利用免疫印迹方法观察白藜芦醇对MCF-7乳腺癌细胞中ERK1/2与AKT信号分子的蛋白表达。结果:白藜芦醇能够明显降低MCF-7乳腺癌细胞增殖能力,该作用呈一定的浓度依赖性关系。在ERK1/2抑制剂PD98059预处理情况下,白藜芦醇对MCF-7乳腺癌细胞增殖抑制效应能明显抑制,PD98059可明显减轻该效应。同时,白藜芦醇明显增加p-ERK1/2蛋白表达,降低p-AKT表达水平,但对ERK1/2与AKT蛋白表达无改变。结论:白藜芦醇能够有效抑制MCF-7乳腺癌细胞增殖,该效应与白藜芦醇对ERK1/2及AKT信号途径的调节有关。      

胰腺癌发生的危险及保护因素

研究发现吸烟、慢性胰腺炎、糖尿病、遗传、乙肝病毒等多种因素都是胰腺癌发生的危险因素,适量运动、白藜芦醇以及维生素等物质的摄入可使胰腺癌发病风险降低.研究胰腺癌的危险及保护因素对于预防胰腺肿瘤发生有重要意义.     

植物提取物抗肿瘤研究进展

 植物提取物是一类重要的抗肿瘤药物,抗肿瘤药物的研究主要集中于白藜芦醇、蓖麻毒素、表没食子儿茶素、冬凌草甲素、胡桃醌、槲皮素、苦参碱、去甲二氢愈创木酸等几种重要的植物提取物。体内外研究表明,植物提取物抗肿瘤的作用机制包括诱导凋亡、细胞毒性作用、诱导再分化、抗肿瘤血管形成和抗侵袭转移等,呈多环节多靶位,部分植物提取物已用于临床前研究。植物提取物抗肿瘤机制的深入研究对肿瘤治疗有重要意义,其完整机制有待进一步研究。     

Resveratrol modulation of signal transduction in apoptosis and cell survival: a mini-review

BACKGROUND: There is mounting evidence in the literature that resveratrol is a promising natural compound for prevention and treatment of a variety of human cancers. This overview summarizes recent studies of the major apoptosis and survival pathways regulated by resveratrol. BIOLOGICAL MECHANISMS: Apoptosis or programmed cell death is a key regulator of tissue homeostasis during normal development and also in adult organism under various conditions including adaptive responses to cellular stress. For example, tissue homeostasis is maintained by tight control of signaling events regulating cell death and survival. Thus, uncontrolled proliferation or failure to undergo cell death is involved in pathogenesis and progression of many human diseases, for example in tumorigenesis or in cardiovascular disorders. Moreover, current cancer therapies primarily act by triggering apoptosis programs in cancer cells. THERAPEUTIC APPLICATIONS: Natural products such as resveratrol have gained considerable attention as cancer chemopreventive or cardioprotective agents and also because of their antitumor properties. Among its wide range of biological activities, resveratrol has been reported to interfere with many intracellular signaling pathways, which regulate cell survival or apoptosis. DISCUSSION: Further insights into the signaling network and interaction points modulated by resveratrol may provide the basis for novel drug discovery programs to exploit resveratrol for the prevention and treatment of human diseases.     

Ataxia–telangiectasia mutated kinase‐mediated upregulation of NKG2D ligands on leukemia cells by resveratrol results in enhanced natural killer cell susceptibility

The powerful activating receptor NKG2D is expressed by natural killer (NK) cells and promotes cytotoxic lysis of cancer cells expressing NKG2D ligands (NKG2D‐Ls). We report the effective induction of NKG2D‐Ls, achieved with the naturally occurring polyphenol resveratrol, in a broad range of leukemia cells. In this study, resveratrol upregulated the NKG2D‐Ls MHC class I chain‐related proteins MICA and MICB, and UL16‐binding proteins ULBP1, ULBP2, and ULBP3 in most of the leukemia cells analyzed. Ligand upregulation induced by resveratrol was impaired by pharmacological and genetic disruption of ataxia–telangiectasia mutated kinase, the main regulator of NKG2D‐L expression. Leukemia cells treated with resveratrol were more susceptible to killing by NK cells than untreated cells, and the enhanced cytotoxicity of NK cells was blocked by treatment of NK cells with anti‐NKG2D mAbs. Interestingly, resveratrol consistently upregulated the NKG2D receptor expression and enhanced NKG2D‐mediated functions in resting NK cells obtained from healthy individuals. Therefore, resveratrol has attractive immunotherapeutic potential.     

Resveratrol induces DNA double-strand breaks through human topoisomerase II interaction

Resveratrol, a stilbene found in grapes and wine, is one of the most interesting natural compound due to its role exerted in cancer prevention and therapy. In particular, resveratrol is able to delay cell cycle progression and to induce apoptotic death in several cell lines. Here we report that resveratrol treatment of human glioblastoma cells induces a delay in cell cycle progression during S phase associated with an increase in histone H2AX phosphorylation. Furthermore, with an in vitro assay of topoisomerase IIα catalytic activity we show that resveratrol is able to inhibit the ability of recombinant human TOPO IIα to decatenate kDNA, so that it could be considered a TOPO II poison.     

Genistein and resveratrol: mammary cancer chemoprevention and mechanisms of action in the rat

The environment, including diet, plays a critical role in a woman’s subsequent risk of breast cancer. Two dietary polyphenols that have received attention from the health and research communities for their ability to protect against breast cancer are: genistein, a component of soy; and resveratrol, a phytoalexin found in red grapes and red wine. We and others have shown that both genistein and resveratrol can protect against mammary cancer in rodents. The timing of exposure to genistein appears critical for its mammary protective effects. It has been reported that genistein early in life causes enhanced mammary gland differentiation, alterations in cell proliferation and apoptosis, and upregulation of tumor-suppressor genes. With resveratrol in the diet, changes in cell proliferation and apoptosis in terminal ductal structures of the mammary gland might help to explain its protective effects. We conclude that genistein and resveratrol can protect against breast cancer by regulating important mammary growth and differentiation pathways.     

Genistein and resveratrol: mammary cancer chemoprevention and mechanisms of action in the rat

The environment, including diet, plays a critical role in a woman's subsequent risk of breast cancer. Two dietary polyphenols that have received attention from the health and research communities for their ability to protect against breast cancer are: genistein, a component of soy; and resveratrol, a phytoalexin found in red grapes and red wine. We and others have shown that both genistein and resveratrol can protect against mammary cancer in rodents. The timing of exposure to genistein appears critical for its mammary protective effects. It has been reported that genistein early in life causes enhanced mammary gland differentiation, alterations in cell proliferation and apoptosis, and upregulation of tumor-suppressor genes. With resveratrol in the diet, changes in cell proliferation and apoptosis in terminal ductal structures of the mammary gland might help to explain its protective effects. We conclude that genistein and resveratrol can protect against breast cancer by regulating important mammary growth and differentiation pathways.     

Dihydroceramide intracellular increase in response to resveratrol treatment mediates autophagy in gastric cancer cells

Resveratrol has both apoptosis and autophagy-promoting activities in different cancer cells. Dihydroceramide is the immediate precursor of the apoptotic mediator ceramide in the de novo sphingolipid synthesis pathway. Here we demonstrate that resveratrol induces autophagy in HGC-27 cells, with no sign of cell death. Autophagy occurs after an increase in dihydroceramides by inhibition of dihydroceramide desaturase. The effects of resveratrol are mimicked by a dihydroceramide desaturase inhibitor. These results demonstrate that resveratrol-induced autophagy occurs with a rise in intracellular dihydroceramide levels as the result of inhibition of dihydroceramide desaturases activity and that dihydroceramide accumulation is responsible for autophagy promotion.