Selective toxicity of compounds naturally present in food toward the transformed phenotype of human colorectal cell line HT29

Abstract

It has previously been observed that allyl isothiocyanate, a compound naturally present in the diet, is more cytotoxic toward the human colorectal adenocarcinoma cell line HT29 in its control transformed state than after exposure to sodium butyrate or to dimethylformamide, which slow growth and induce differentiation (detransformation). In the present study, a range of other dietary compounds were assayed for such selective toxicity. These compounds were chosen as constituents of foodstuffs that have been identified from epidemiologic studies as being potentially antitumorigenic and also as having anticarcinogenic activity in experimental models. Benzyl and phenethyl isothiocyanate, benzyl thiocyanate, and quercetin showed decreased toxicity towards HT29 after detransformation of the cells by one or both treatments, whereas no change was observed in the sensitivity to diallyl sulfide or diallyl disulfide. It is proposed that the presence of such selectively toxic compounds in the diet may inhibit the development of tumors by interfering with the growth of preneoplastic lesions while having little effect on normal cells. The cumulative effects of these inhibitions may contribute to the chemopreventive properties of the parent foodstuffs observed in epidemiologic studies.

Preclinical Evaluation of 4-Methylthiobutyl Isothiocyanate on Liver Cancer and Cancer Stem Cells with Different p53 Status

“…So far, the specific cytotoxicity of ITC to cancer cells has been almost exclusively hypothesized based on results from transformed and non-transformed cell lines. As an example, differentiated HT29 human colon carcinoma cells were less sensitive to allyl ITC, BITC or PEITC as compared to the de-differentiated cells [45], [46]. SFN was also shown to be non-cytotoxic to differentiated colon carcinoma (CaCo2) cells, although it killed the undifferentiated counterpart [47].…”

Induction of histone acetylation in mouse erythroleukemia cells by some organosulfur compounds including allyl isothiocyanate

“…There is evidence that allyl isothiocyanate is more growth inhibitory for the transformed than the differentiated phenotype of colon cancer cells. 10,17 There is extensive literature suggesting that the extent of histone acetylation can influence growth and differentiation of cancer cells. 18 -20 As a first approximation it seems that differentiation of cancer cells is favored by agents that increase histone acetylation.…”

Sulphur‐Containing Compounds

“…These can be metabolized in the presence of nitrite to form mutagenic N -nitroso compounds (Wakabayashi et al 1985;Tiedink et al, 1990). 2-Propenyl and phenylethyl isothiocyanates have also been shown to induce clastogenic changes in mammalian cell lines (Musk et al 1995). However, considerable amounts of epidemiological data and experimental studies suggest that glucosinolate and their hydrolytic products act as anti-carcinogenic agents in the diet.…”