Abstract
ABSTRACTThe inhibitory potential of sulforaphane against cancer has been suggested for different types of cancer, including ovarian cancer. We examined whether this effect is mediated by mitogen-activated protein kinase (MAPK) and reactive oxygen species (ROS), important signaling molecules related to cell survival and proliferation, in ovarian cancer cells. Sulforaphane at a concentration of 10 μM effectively inhibited the growth of cancer cells. Use of specific inhibitors revealed that activation of MAPK pathways by sulforaphane is unlikely to mediate sulforaphane-induced growth inhibition. Sulforaphane did not generate significant levels of intracellular ROS. Pretreatment with thiol reducers, but not ROS scavengers, prevented sulforaphane-induced growth inhibition. Furthermore, diamide, a thiol-oxidizing agent, enhanced both growth inhibition and cell death induced by sulforaphane, suggesting that the effect of sulforaphane on cell growth may be related to oxidation of protein thiols or change in cellular redox status. Our data indicate that supplementation with thiol-reducing agents should be avoided when sulforaphane is used to treat cancer.
Highlights
Sulforaphane is a dietary isothiocyanate that is present as a glucosinolate precursor in cruciferous vegetables, including broccoli and cauliflower
Ovarian cancer cells were treated with sulforaphane at concentrations ranging from 0 to 100 μM, and the effect on cell growth was evaluated
We examined how these concentrations of sulforaphane affect the growth of non-cancer cells
Summary
Sulforaphane is a dietary isothiocyanate that is present as a glucosinolate precursor in cruciferous vegetables, including broccoli and cauliflower. Epidemiological studies have suggested that a high level of consumption of cruciferous vegetables reduces the risk of many types of cancer [4,5,6], and the protective effect of crucifers against cancer has been attributed to their high glucosinolate content [1,4]. Sulforaphane has been demonstrated to induce phase II detoxification and antioxidant enzymes [8] and to inhibit phase I enzymes that activate pro-carcinogens [9]. Administration of sulforaphane inhibits and/or retards tumorigenesis induced by carcinogens in animal models [10,11]. In addition to its preventive effect on cancer, sulforaphane has recently been shown to inhibit the growth of various types of cancer cells by modulating multiple pathways related to cancer progression [7,12]
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