Cell death in the colorectal cancer cell line HT29 in response to glucosinolate metabolites

Authors


Abstract

Glucosinolate breakdown products are potential anti-carcinogenic phytochemicals derived from cruciferous vegetables. This study compared the induction of apoptosis in colorectal adenocarcinoma cells (HT29) by four isothiocyanates (ITC) benzyl-ITC, allyl-ITC (AITC), phenylethyl-ITC (PEITC) and methylsulphinylbutyl-ITC (sulforaphane). Apoptosis was determined by analysis of DNA content, annexin V staining, gel electrophoresis, CPP32 expression/inhibition and the histological appearance of nuclei. In terms of their ability to reduce adherent cell number, the relative potency of ITCs was BITC = AITC > PEITC ≫ sulforaphane. Non-adherent cells from test flasks showed less evidence of apoptosis than those grown under control conditions. Our results implied that ITCs first blocked cells at G2/M and subsequently caused a loss in adherence which was not reduced by caspase inhibitors or by pre-loading the cells with an antioxidant, the GST mimic Ebselen. This suggests that the primary action of ITCs is to block rapidly proliferating cancer cells in G2/M. In this particular p53 null cell line, loss of cell adherence was not part of an apoptotic process, nor did it involve free radical signaling pathways.

© 2001 Society of Chemical Industry.

Ancillary