Chemoprevention by isothiocyanates and their underlying molecular signaling mechanisms

Young Sam Keum, Woo Sik Jeong, A. N. Tony Kong

Research output: Contribution to journalReview articlepeer-review

236 Scopus citations

Abstract

Chemoprevention is a cancer preventive strategy to inhibit, delay or reverse carcinogenesis using naturally occurring or synthetic chemical agents. Numerous epidemiological studies as well as experimental animal studies clearly demonstrate that high intake of cruciferous vegetables protects against tumorigenesis. Thus, cruciferous vegetables have been of great interest for potential use in the chemoprevention of cancer. Cruciferous vegetables are rich source of glucosinolates, which are degraded into isothiocyanates by enzymatic action of plant-specific myrosinase or intestinal flora in the body. It appears that significant portion of the chemopreventive effects of isothiocyanates may be associated with the inhibition of the metabolic activation of carcinogens by cytochrome P450s (Phase I), coupled with strong induction of Phase II detoxifying and cellular defensive enzymes. Inductions of Phase II cellular enzymes are largely mediated by the antioxidant responsive element (ARE), which is regulated by the transcriptional factor, Nrf2. Additional potent regulatory mechanisms of Nrf2 include the different signaling kinase pathways (MAPK, PI3K, PKC and PERK) as well as other non-kinase dependent mechanisms. Moreover, apoptosis and cell cycle perturbations appear to be yet another potential chemopreventive mechanisms elicited by isothiocyanates, especially with respect to the effects on pre-initiated or initiated tumor cells. Finally, modulation of other critical signaling mediators, including the NF-κB and AP-1 by a wide array of chemopreventive agents including isothiocyanates may also contribute to the overall chemopreventive mechanisms.

Original languageEnglish (US)
Pages (from-to)191-202
Number of pages12
JournalMutation Research - Fundamental and Molecular Mechanisms of Mutagenesis
Volume555
Issue number1-2 SPEC. ISS.
DOIs
StatePublished - Nov 2 2004

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Genetics
  • Health, Toxicology and Mutagenesis

Keywords

  • Chemoprevention
  • Signaling kinase pathways
  • Tumorigenesis

Fingerprint Dive into the research topics of 'Chemoprevention by isothiocyanates and their underlying molecular signaling mechanisms'. Together they form a unique fingerprint.

Cite this