Chemoprotection by sulforaphane: keep one eye beyond Keap1.
Sulforaphane (SFN) is an isothiocyanate found in cruciferous vegetables, with particularly high levels detected in broccoli and broccoli sprouts. Over a decade ago, this phytochemical was identified as a likely chemopreventive agent based on its ability to induce Phase 2 detoxification enzymes, as well as to inhibit Phase 1 enzymes involved in carcinogen activation. Considerable attention has focused on SFN as a 'blocking' agent, with the ability to modulate the Nrf2/Keap1 pathway, but recent evidence suggests that SFN acts by numerous other mechanisms. SFN induces cell cycle arrest and apoptosis in cancer cells, inhibits tubulin polymerization, activates checkpoint 2 kinase, and inhibits histone deacetylase activity. The latter findings suggest that SFN may be effective during the post-initiation stages of carcinogenesis, as a 'suppressing' agent. Moreover, pharmacological administration of SFN may be a promising therapeutic approach to the treatment of cancers, including those characterized by increased inflammation and involving viral or bacterial-related pathologies. The present review discusses the more widely established chemoprotective mechanisms of SFN, but makes the case for additional work on mechanisms that might be of importance during later stages of carcinogenesis, beyond Keap1.
Myzak
Melinda C
MC
Linus Pauling Institute, Oregon State University, Corvallis, OR 97331, USA.
Dashwood
Roderick H
RH
D016588:Anticarcinogenic Agents / Q000627:therapeutic use*; D002453:Cell Cycle / Q000187:drug effects*; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D017879:Isothiocyanates; D000072019:Kelch-Like ECH-Associated Protein 1; D009369:Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D011506:Proteins / Q000378:metabolism*; D015398:Signal Transduction; D013454:Sulfoxides; D013861:Thiocyanates / Q000627:therapeutic use*
D016588:Anticarcinogenic Agents; D047908:Intracellular Signaling Peptides and Proteins; D017879:Isothiocyanates; C431364:KEAP1 protein, human; D000072019:Kelch-Like ECH-Associated Protein 1; D011506:Proteins; D013454:Sulfoxides; D013861:Thiocyanates; C016766:sulforaphane