Inhibition of skin tumor initiation, promotion, and progression by antioxidants and related compounds

Abstract

Antioxidants have been shown to inhibit the induction of cancer by a wide variety of chemical carcinogens and radiation at many target sites in mice, rats, hamsters, and man. Evidence is accumulating that suggests that free radicals are important in all stages of chemical carcinogenesis. Both carcinogens and tumor promoters have also been shown to decrease the cellular activity of superoxide dismutase and catalase. A number of antioxidants and related compounds were tested to determine if they would inhibit either skin tumor initiation, promotion, or progression. In terms of skin tumor initiation, compounds such as BHT, vitamins E and C, and CuDIPS have been found to inhibit DMBA skin tumor initiation. The mechanism of action of these compounds appears to be related to their effect on the metabolism of DMBA, as BHT and CuDIPS do not inhibit the initiating activity of BP-diol-epoxide and MNNG. Although several antioxidants do inhibit skin tumor initiation by procarcinogens, antioxidants are in general much more effective inhibitors of skin tumor promotion. BHT, BHA, parahydroxyanisole, disulfiran, and vitamins E and C as well as many other antioxidants are very effective inhibitors of skin tumor promotion. We also determined the effect of free radical scavengers on the progression process. Of the agents tested, glutathione and N-acyl dehydroalamines were the most effective in reducing carcinoma incidence. Diethyl maleate, a chemical that reduces glutathione levels, was effective in enhancing progression. In addition, overexpression of gamma-glutamyltranspeptidase (GGT), which leads to a reduction in cellular glutathione levels, also enhances progression.(ABSTRACT TRUNCATED AT 250 WORDS)

Detoxifying Cancer Causing Agents to Prevent Cancer

“…These compounds have been shown to alter specific metabolic pathways, including phase I and phase II enzyme mediated pathways, in bringing about inhibition of carcinogenesis in different tissues. 2,24 All these compounds appear to have the common feature that they have been shown to induce the activity of glutathione S-transferases in specific tissues. 2,24 Many of these compounds appear to have actions that would place them in mechanism (c) above.…”

“…For example, one may chose an agent that appears to work primarily by mechanism (a) above, for example, ellagic acid. 2,24 This compound has been shown to block cytochrome P450 enzymes involved in the metabolic activation of polycyclic aromatic hydrocarbons. On the other hand, ellagic acid appears to work also by scavenging electrophilic carcinogenic intermediates.…”

“…One of the goals of current studies in cancer prevention is to determine the mechanisms of synergistic action of the natural source compounds, known to inhibit one or more stages of carcinogenesis, that is, initiation and promotion/progression. 2,24 The basic theory underlying these studies is that concurrent treatment with various natural source inhibitors of different stages of carcinogenesis results in synergistic effects, leading to more efficient prevention of cancer.…”

“…2,24,25 The mouse skin model, which represents one of the best understood experimental models of multistage carcinogenesis, has permitted the resolution of three distinct stages: initiation, promotion, and progression. 21,22 It is now apparent that the cellular evolution to malignancy involves the sequential alteration of proto-oncogenes 26 and/or tumor suppressor genes, 27 whose gene products participated in critical pathways for the transduction of signals and/or regulation of gene expression.…”

Self-Organization of Silver-Core Bimetallic Nanoparticles and Their Application for Catalytic Reaction

“…For example, hydroquinone, a metabolite of carcinogenic benzene, causes DNA damage via H 2 O 2 generation . Many studies have addressed the role of antioxidants, such as vitamins (Slaga, 1995;Sohmiya et al, 2004) and catechins (Weyant et al, 2001), in protection against cancers and cardiovascular diseases. These antioxidants can scavenge reactive oxygen species and protect against cancer occurrence.…”