6-(Methylsulfonyl) hexyl isothiocyanate as potential chemopreventive agent: Molecular and cellular profile in leukaemia cell lines

Abstract

Numerous laboratory and epidemiological studies show that the risk of developing several types of cancer can be reduced with the employment of natural substances that act with multiple mechanisms. In this context, an important role is played by the isothiocyanates. Recently, 6-(methylsulfonyl)hexyl isothiocyanate (6-MITC), present in the root of Wasabia Japonica, has stimulated the interest of researchers as a chemopreventive agent. In this particular study we have focused on evaluating 6-MITC's in vitro cytotoxic, cytostatic and cytodifferentiating activities, as well as its pro-apoptotic potential. These effects were investigated by way of flow cytometric analysis of Jurkat and HL-60 cells as well as of healthy lymphocytes extracted from the blood of AVIS donors, in order to verify a potential selectivity of action. The results demonstrate that 6-MITC exerts a stronger cytotoxic effect on tumour cells than on healthy cells. The apoptosis induction exerted by 6-MITC on transformed cells is triggered by an extrinsic pathway, as demonstrated by the statistically significant increase in the percentage of cells with activated caspase-8. It was also observed that 6-MITC is able to limit tumour growth by slowing down and blocking the cell cycle of Jurkat and HL-60 cells respectively, in a dose- and time-related manner, while exerting no activity of any kind on the replication of healthy cells. Finally, by measuring the expression levels of CD-14 and CD-15, 6-MITC showed the ability to induce cytodifferentiation of HL-60 cells into macrophage and granulocytic phenotypes.