Role of Reactive Oxygen Intermediates in Cellular Responses to Dietary Cancer Chemopreventive Agents

Epidemiological studies continue to support the premise that diets rich in fruits and vegetables may offer protection against cancer of various anatomic sites. This correlation is quite persuasive for vegetables including Allium (e. g., garlic) and cruciferous (e. g., broccoli and watercress) vegetables. The bioactive food components responsible for the cancer chemopreventive effects of various edible plants have been identified. For instance, the anticancer effects of Allium and cruciferous vegetables are attributed to organosulfur compounds (e. g., diallyl trisulfide) and isothiocyanates (e. g., sulforaphane and phenethyl isothiocyanate), respectively. Bioactive food components with anticancer activity are generally considered to be antioxidants due to their ability to modulate expression/activity of antioxidative and phase 2 drug-metabolizing enzymes and scavenging free radicals. At the same time, more recent studies have provided convincing evidence to indicate that certain dietary cancer chemopreventive agents cause generation of reactive oxygen species (ROS) to trigger signal transduction culminating in cell cycle arrest and/or programmed cell death (apoptosis). Interestingly, the ROS generation by some dietary anticancer agents is tumor cell specific and does not occur in normal cells. This review summarizes experimental evidence supporting the involvement of ROS in cellular responses to cancer chemopreventive agents derived from common edible plants. Abbreviations AITC:allyl isothiocyanate ARE:antioxidant response element BITC:benzyl isothiocyanate DAS:diallyl sulfide DADS:diallyl disulfide DATS:diallyl trisulfide DR5:death receptor 5 ERK:extracellular signal-regulated kinase ITCs:isothiocyanates JNK:c-Jun N-terminal kinase MMP:mitochondrial membrane potential NAC: N -acetylcysteine OSCs:organosulfur compounds PEITC:phenethyl isothiocyanate ROS:reactive oxygen species SAC: S -allylcysteine SAMC: S -allylmercaptocysteine