Role of 4-hydroxynonenal in chemopreventive activities of sulforaphane

Abstract

Chemoprevention of cancer via herbal and dietary supplements is a logical approach to combat cancer and presently it is an attractive area of research investigations. Over the years, the use of isothiocyanates, such as sulforaphane (SFN) found in cruciferous vegetables, has been advocated as chemopreventive agents and their efficacy has been demonstrated in cell lines and animal models. In-vivo studies with SFN suggest that besides protecting normal healthy cells from environmental carcinogens it also exhibits cytotoxicity and apoptotic effects against various cancer cell types. Among several mechanisms for the chemopreventive activity of SFN against chemical carcinogenesis, its effect on drug metabolizing enzymes that causes activation/ neutralization of carcinogenic metabolites is well established. Recent studies suggest that SFN exerts its selective cytotoxicity to cancer cells via reactive oxygen species (ROS)-mediated generation of lipid peroxidation (LPO) products particularly 4-hydroxynonenal (HNE). Against the background of the known biochemical effects of SFN on normal and cancer cells, in this article we have reviewed the underlying molecular mechanisms responsible for the overall chemopreventive effects of SFN focusing on the role of HNE in these mechanisms that may also contribute to its selective cytotoxicity to cancer cells.

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

“…Other studies also showed that SFN treatment significantly reduces cell viability of various cancer cells i.e., human leukemia T-cells, breast, pancreatic, lymphoblastoid and glioma cancer cells in a dose-dependent manner (Fimognari et al, 2002;Misiewicz et al, 2004;Meeran et al, 2010;Huang et al, 2012;Li et al, 2012). Interestingly, SFN has a safe cytotoxicity profile towards the normal cells thus it can be utilized in the development of safe cancer treatment strategies (Sharma et al, 2012).…”

Sulforaphane induces Nrf2 and protects against CYP2E1-dependent binge alcohol-induced liver steatosis

“…Chemical activation of Nrf2 by sulforaphane was studied in hopes of finding an effective pharmacological method as possible therapy against ethanol toxicity. The chemopreventive activites of sulforaphane have been recently reviewed [57]. Besides antioxidant activity largely via activation of Nrf2, sulforaphane can decrease phase 1 cytochrome P450 enzymes, increase phase II enzymes, decrease HIF alpha and COX 2 among other enzymes [57].…”

“…The chemopreventive activites of sulforaphane have been recently reviewed [57]. Besides antioxidant activity largely via activation of Nrf2, sulforaphane can decrease phase 1 cytochrome P450 enzymes, increase phase II enzymes, decrease HIF alpha and COX 2 among other enzymes [57]. Sulforaphane has been shown to lower the pathology and decrease oxidative stress in livers of mice fed a methionine choline deficient diet in which steatohepatitiis occurs [58].…”

Regulatory roles of glutathione-S-transferases and 4-hydroxynonenal in stress-mediated signaling and toxicity

“…During the past two decades, the role of HNE and GSTs in the mechanisms of stress-induced signaling and toxicity has been extensively studied by us [6,28–37,90,91] and by others [3,8,27,92,93]. Our studies reveal that over-expression of GSTA1-1 and GSTA2-2 in cells provide protection from cell death and apoptosis caused by radiation, H 2 O 2 , super oxide anions, chemicals such as doxorubicin and naphthalene [28–30, 87].…”