Laboratory of Diet, Nutrition and Cancer, Department of Food and Experimental Nutrition, University of São Paulo, São Paulo, Brazil.
Curr Cancer Drug Targets. 2012 Nov 1;12(9):1173-90. doi: 10.2174/156800912803987986.
Bioactive food components (BFACs) represent promising candidates for liver cancer chemoprevention. Among them, isoprenic derivatives (carotenoids, retinoids, perillyl alcohol, limonene, geraniol, farnesol, geranylgeraniol and β- ionone) can be highlighted. The relevance of animal models for the investigation of chemopreventive agents is supported by comparative functional genomic studies that reinforce the similarities between rodent and human hepatocarcinogenesis. Thus, characterization of BFACs in animal models as blocking and/or suppressing agents allows the establishment of the theoretical basis for the development of chemoprevention strategies. Dietary isoprenic derivatives actions on hepatocarcinogenesis may involve a block in carcinogen activation, induction of phase 2 enzymes and an antioxidant activity, as well as interference with cellular processes including cell communication, proliferation, apoptosis, differentiation and remodeling of preneoplastic lesions. Dietary isoprenic derivatives modulate molecular targets including HMG-CoA-reductase, Rho, nuclear receptors, c-myc, connexin 43, NF-κB and Nrf2. Several networks related to these targets are altered in early phases of hepatocarcinogenesis. This emphasizes the importance of such agents for the chemoprevention of hepatocellular carcinoma. Combinations of isoprenic derivatives or of these substances with other BFACs classes should be further investigated. Also, toxicity and bioavailability and pharmacokinetic aspects of these derivatives represent relevant issues in their development as chemopreventive agents. One major current limitation of the adoption of dietary isoprenic derivatives for liver cancer chemoprevention is the challenge in overcoming the initial preclinical phase in agent development. Dietary isoprenic derivatives that present liver cancer chemopreventive properties should be further explored in clinical trials, begining with the phase 0 approach.
生物活性食品成分 (BFACs) 是肝癌化学预防的有前途的候选物。其中，异戊二烯衍生物（类胡萝卜素、视黄醇、紫苏醇、柠檬烯、香叶醇、法呢醇、香叶基香叶醇和β-紫罗兰酮）可以被突出强调。动物模型在化学预防剂研究中的相关性得到了比较功能基因组研究的支持，这些研究加强了啮齿动物和人类肝癌发生之间的相似性。因此，在动物模型中对 BFACs 作为阻断和/或抑制剂的特征描述允许为化学预防策略的发展建立理论基础。膳食异戊二烯衍生物对肝癌发生的作用可能涉及致癌物激活、诱导 2 相酶和抗氧化活性的阻断，以及对细胞过程的干扰，包括细胞通讯、增殖、凋亡、分化和癌前病变的重塑。膳食异戊二烯衍生物调节分子靶点，包括 HMG-CoA 还原酶、Rho、核受体、c-myc、连接蛋白 43、NF-κB 和 Nrf2。与这些靶点相关的几个网络在肝癌发生的早期阶段发生改变。这强调了这些剂在肝细胞癌化学预防中的重要性。异戊二烯衍生物或这些物质与其他 BFACs 类别的组合应进一步研究。此外，这些衍生物的毒性、生物利用度和药代动力学方面是其作为化学预防剂开发的相关问题。采用膳食异戊二烯衍生物进行肝癌化学预防的一个主要当前限制是在代理开发的初始临床前阶段面临的挑战。具有肝癌化学预防特性的膳食异戊二烯衍生物应在临床试验中进一步探索，从 0 期方法开始。
