Chemoprotection by sulforaphane: Keep one eye beyond Keap1

Abstract

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 postinitiation 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.

Sulforaphane Inhibits Growth of Human Breast Cancer Cells and Augments the Therapeutic Index of the Chemotherapeutic Drug, Gemcitabine

“…Therefore it is coming up as an economical, easily available, and novel approach to cancer treatment and management (Karikas, 2010). Sulforaphane is an isothiocyanate, found in cruciferous vegetables, such as broccoli, kale, and cauliflower displays significant chemopreventive activity resulting from its inhibition of carcinogen-activating enzymes and induction of detoxification enzymes affecting carcinogen metabolism and disposition and by modulating epigenetic machinery (Barcelo et al, 1996;Basten et al, 2002;Myzak et al, 2006;Gibbs et al, 2009).…”

Antiproliferative activity of sulforaphane in Akt-overexpressing ovarian cancer cells

“…Our studies show that the inhibition of clonogenicity was observed with much lower doses than for the inhibition of Akt. It is therefore possible that Aktindependent prosurvival pathways, such as extracellular signal-regulated kinase/c-Jun-NH 2 -kinase/p38 may be responsible for inhibition in the clonogenic ability and long-term survival of ovarian cancer cells, which needs investigation (20,21).…”

NF-κB and Nrf2 as prime molecular targets for chemoprevention and cytoprotection with anti-inflammatory and antioxidant phytochemicals

“…It activates Nrf2, possibly by modifying the sensor cysteines present in Keap1 [27,28]. While considerable attention has focussed on sulforaphane as a ''blocking'' agent, with the ability to modulate Nrf2-Keap1 signaling, it also exerts anti-inflammatory effects [29]. Thus, sulforaphane inhibited lipopolysaccharideinduced activation of NF-jB and COX-2 expression in cultured mouse macrophages [30].…”