Abstract

Sulforaphane (SFN), one of naturally occurring isothiocyanates (ITCs), has huge cancer chemopreventive potential. It modulates cell death, cell cycle, angiogenesis, susceptibility to carcinogens, invasion and metastasis and possesses antioxidant activities. It functions as an inhibitor of phase I enzymes and also as an inducer of phase II detoxification enzymes through different ways. NF-E2- related factor-2(Nrf-2), as well as mitogen-activated protein kinase (MAPK), is regulated by SFN. Intriguingly, strong evidence has showed the dark side of Nrf-2: stable upregulation of Nrf-2-mediated survival pathway would protect cancer cells from a subset of chemotherapeutic agents tested. This suggested that overexpression of Nrf-2 resulted in enhanced resistance of cancer cells to chemotherapeutic agents. Hence, future studies will focus on clarifying the exact time and dose of SFN to modulate the Nrf-2 signal pathway during chemotherapy and the efficacy of coadministration of Nrf-2 modulators during chemotherapy in order to make full use of the beneficial effect of this agent while eliminating the potential side effects.

Keywords: Anti-Cancer, Chemopreventive agent, Chemoresistance, Combination therapy, Isothiocyanates, Signaling pathway, Sulforaphane, Systemic toxicity, Glueosinolates, pancreatic