Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
9031149 | Food and Chemical Toxicology | 2005 | 8 Pages |
Abstract
Despite strong evidence that isothiocyanates (ITCs) inhibit cancer development, there are also reports that some of them induce or promote carcinogenesis. The molecular basis of the latter is largely unknown. We report here that all three ITCs that caused urinary bladder cancer in rats, including allyl ITC, benzyl ITC, and phenethyl ITC, increased the transactivation of activator protein 1 (AP-1) and AP-1 DNA binding in human bladder cancer UM-UC-3 cells. Amongst all Fos and Jun family members examined, only were the levels of c-Jun and Fra-2 consistently elevated by the ITCs. However, whereas c-Jun was identified as the predominant component in the AP-1 DNA binding complex, Fra-2 was not detected, suggesting that c-Jun may be mainly responsible for ITC-induced AP-1 activation. c-Jun was also induced by the ITCs in other bladder cancer cell lines (both human and rat) and by their N-acetylcysteine derivatives-their main urinary metabolites. c-Jun induction by the ITCs appears to involve both transcriptional activation and protein phosphorylation; the latter resulted from activation of c-Jun N-terminal kinase by the ITCs. Because c-Jun has been implicated in cancer development, including human bladder cancer, our data suggest that c-Jun activation may play an important role in ITC-induced bladder carcinogenesis.
Keywords
AP-1BITC, benzyl isothiocyanateITCs, isothiocyanatesPEITC, phenethyl isothiocyanateActD, actinomycin DAITC, allyl isothiocyanateAP-1, activator protein 1EMSA, electrophoresis mobility shift assayGAPDH, glyceraldehyde-3-phosphate dehydrogenaseJNK, c-Jun N-terminal kinaseNAC, N-acetylcysteinePMSF, phenylmethylsulfonyl fluorideACN, acetonitrileIsothiocyanateBladder cancerCarcinogenesis
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Authors
J. Li, S. Yao, Y. Zhang,