Abstract
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.
Keywords: Bioactive food components, cellular targets, chemoprevention, dietary isoprenic derivatives, liver cancer, molecular targets, retinoid X receptors, retinoic acid receptors, resistant hepatocyte, preneoplastic lesions, nonalcoholic steatohepatitis, diethylnitrosamine, farnesoid X receptor, gamma glutamyl transpeptidase, hepatocellular carcinoma
Current Cancer Drug Targets
Title:Chemoprevention of Hepatocarcinogenesis with Dietary Isoprenic Derivatives: Cellular and Molecular Aspects
Volume: 12 Issue: 9
Author(s): Thomas Prates Ong, Monica Testoni Cardozo, Aline de Conti and Fernando Salvador Moreno
Affiliation:
Keywords: Bioactive food components, cellular targets, chemoprevention, dietary isoprenic derivatives, liver cancer, molecular targets, retinoid X receptors, retinoic acid receptors, resistant hepatocyte, preneoplastic lesions, nonalcoholic steatohepatitis, diethylnitrosamine, farnesoid X receptor, gamma glutamyl transpeptidase, hepatocellular carcinoma
Abstract: 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.
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Prates Ong Thomas, Testoni Cardozo Monica, de Conti Aline and Salvador Moreno Fernando, Chemoprevention of Hepatocarcinogenesis with Dietary Isoprenic Derivatives: Cellular and Molecular Aspects, Current Cancer Drug Targets 2012; 12 (9) . https://dx.doi.org/10.2174/15680096112091173
DOI https://dx.doi.org/10.2174/15680096112091173 |
Print ISSN 1568-0096 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-5576 |
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