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Cancer chemoprevention by phytochemicals:potential molecular targets,biomarkers and animal models

Acta Pharmacologica Sinica 2007年第9期28卷 1409-1421页

作者： Ki Han KWON Avantika BARVe Siwang Yu Mou-Tuan HUANG Ah-Ng Tony KONG Center for Cancer Prevention Research Department of Pharmaceutics Center for Cancer Prevention Research Graduate Program in Pharmaceutical Science Center for Cancer Prevention Research Susan Lehman Cullman Laboratory for Cancer Research Center for Cancer Prevention Research Department of Pharmaceutics Department of Chemical Biology Ernest Mario School of Pharmacy RutgersThe State University of New JerseyPiscatawayNJ 08854USA

Recent studies have strongly indicated that certain daily-consumed dietaryphytochemicals could have cancer protective effects against transgenic mice can-cer models and cancers mediated by carcinogens,irradiations and carcinogenicmetabolites derived from exogenous or endogenous *** cancer-protec-tive effects elicited by these dietary compounds are believed to be due at least inpart to the induction of cellular defense systems including the detoxifying andantioxidant enzymes system,as well as the inhibition of anti-inflammatory andanti-cell growth signaling pathways culminating in cell cycle arrest and/or cell-death,in this review,we summarize the potential mechanisms including the modu-lation of nuclear factor kappaB (NF-kB),cyclooxygenases-2 (COX-2),activatorprotein-1 (AP-1),mitogen-activated protein kinases (MAPKs) and the inductionof phase Ⅱ cellular detoxifying and antioxidant enzymes mediated mainly by theantioxidant response elements (ARe) within the promoter regions of these genesthrough nuclear factor-erythroid 2-related factor 2 (Nff2),a member of the Cap‘n’collar (CNC) family of the basic region-leucine zipper transcription ***,we also review several animal models of carcinogenesis and cancerchemopreventive efficacy studies of these animal models using dietarychemopreventive ***,we discuss the cellular signaling cascadesmediated by Nrf2,NF-kB,AP-1,MAPKs and COX-2,which have been consideredto play pivotal roles in tumor initiation,promotion and progression processes,and could be promising molecular targets for the design of drugs targeting cancerprevention and therapy.

关键词： chemoprevention dietary cancer chemopreventive compounds nuclear factor e2related factor 2 nuclear factor-kappaB activator protein-l mitogen-activated protein kinases

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