6-(Methylsulfonyl) hexyl isothiocyanate induce autophagy in leukemia cell lines

Introduction: Autophagy is a fundamental catabolic process of cellular survival through which the cell degrades and recycles cellular components. However, the alteration of its normal mechanism may be responsible for the development of many diseases, such as cancer. The role of autophagy in cancer is extremely complex; on the one hand, in the early stages of neoplastic transformation it can act as a tumor suppressor avoiding the accumulation of proteins, damaged organelles and reactive oxygen species; on the other hand, during the advanced stage of cancer, autophagy is exploited by cancer cells to survive under starved. Numerous substances of natural origin have been shown to have chemopreventive activity and in particular, isothiocyanates are of great interest, between these, more recently the 6-(Methylsulfonyl) hexyl isothiocyanate (6-MITC) attracted the attention of researchers. Studies conducted in our laboratories and recently published demonstrating that 6-MITC is able to exhibit cytotoxic, cytostatic, and cytodifferentiation effects on different leukemic cell lines. These encouraging results stimulate us to continue research investigating other possible potentials. In this context it is extremely interesting to evaluate the modulation of the autophagic process by 6-MITC and the related pathways, with particular attention to ROS-autophagy-cancer interconnection. Materials and Methods: Flow cytometric analysis of Jurkat and HL-60 cells treated with 6-MITC 0-8 M and 0-16M respectively for 20h allowed to evaluate the autophagy mechanism. Subsequently, to better characterize the interconnection between autophagy and oxidative stress the level of DCF, MitoPY, HE, MitoSOX, DHR123, MBC were also evaluated. At the end, in order to extended us previous experience, the data has been confirmed through InCell Analyzer 2000. Results: 6-MITC induced autophagy in Jurkat and HL-60 cells at the highest concentration tested. The levels of intracellular hydrogen peroxide (DCF) increase in a dose dependent manner in both cells line while the levels of mitochondrial hydrogen peroxide (MitoPY) only in HL-60. For the other markers no statistically significant increase was observed. Conclusion: Our data suggest that 6-MITC might be considered an interesting chemopreventive agent. The isothiocyanate is able to induce autophagy through ROS generation and in particular through the production of hydrogen peroxide. These first results encourage the conduct of further studies to learn more about the interconnection oxidative stress, autophagy and cancer.