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.
Highlights
In the late 1970’s Dr Sporn coined the scientific term “chemoprevention” to represent the possible prevention, halting or reversing of the cancerogenic process through the use of synthetic or natural compounds [1,2,3]
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
The Jurkat and HL-60 cells were treated for 24h, 48h and 72h with 6-(methylsulfonyl)hexyl isothiocyanate (6-MITC) at concentrations of 0 to 64μM while the peripheral blood lymphocytes (PBL) cells were treated for 24h
Summary
In the late 1970’s Dr Sporn coined the scientific term “chemoprevention” to represent the possible prevention, halting or reversing of the cancerogenic process through the use of synthetic or natural compounds [1,2,3]. Apoptosis, a physiological process of programmed cell death that plays a key role in homeostasis, is suppressed in many cancer cells. Restoring this ability, is one of the most important strategies for fighting cancer [6,7,8,9]. Phytochemicals derived from edible and medicinal plants have been extensively studied for cancer chemoprevention thanks to their demonstrated ability to modulate the enzymes involved in xenobiotic activation/detoxification, to inhibit cell proliferation and/or to induce apoptosis and the www.impactjournals.com/oncotarget differentiation of neoplastic cells [10,11,12,13]. In recent years, growing interest has been focused on isothiocyanates (ITCs), the main pharmacologically active ingredients of cruciferous vegetables that are able to modulate a large number of cancer-related targets including cytochrome P450 enzymes, proteins involved in the antioxidant response, tumorigenesis, apoptosis, the cell cycle and metastasis [16, 17]
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