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.

Wasabi 6‐(methylsulfinyl)hexyl isothiocyanate induces apoptosis in human colorectal cancer cells through p53‐independent mitochondrial dysfunction pathway

“…1C). This result is different from that in leukemia cells [35], in which there was no significant change in total protein level of P53 from 24 to 48 h in 6-MSITC-treated cells. On the other hand, treatment with sulforaphane, an analog of 6-MSITC, also increased the expression level of P53 in prostate cancer cells [36] and melanoma cells [37], but not in leukemia cells [38].…”

“…Additionally, death receptors are expected as targets for cancer therapy, because they have capability of inducing apoptosis in cancer cells independent with P53 . 6‐(Methylsulfinyl)hexyl isothiocyanate has reported to induce extrinsic apoptosis via caspase‐8 but not mitochondrial intrinsic apoptosis in leukemia cell lines . In this study, we demonstrated that 6‐MSITC had potency to induce both intrinsic apoptosis and extrinsic apoptosis, independent of p53 status.…”

Differential Pharmacological Activities of Oxygen Numbers on the Sulfoxide Moiety of Wasabi Compound 6-(Methylsulfinyl) Hexyl Isothiocyanate in Human Oral Cancer Cells

“…6-MITC has many functions, including neuroprotection [ 18 ], anti-inflammation [ 19 ], anti-pulmonary metastasis [ 1 ], chemoprevention [ 2 , 20 ], and cancer prevention [ 3 , 21 , 22 ]. The mechanisms of 6-MITC inhibit tumor growth through the disruption of mitochondrial function or the inhibition of the NF-κB pathway by abrogating the PI3K/AKT pathway to induce apoptosis [ 22 , 23 ] and sensitizing the anti-tumor agent to augment cell killing [ 17 ].…”

Wasabi Compound 6-(Methylsulfinyl) Hexyl Isothiocyanate Induces Cell Death with Coexisting Mitotic Arrest and Autophagy in Human Chronic Myelogenous Leukemia K562 Cells

“…A naturally-occurring compound, 6-(methylsulfinyl) hexyl isothiocyanate (6-MITC), was isolated from Wasabia japonica (wasabi), a pungent spice widely used in Japanese food. Several biological activities of 6-MITC have been reported, such as anti-inflammatory [17,18], neuroprotective [19,20], anti-cancer [21][22][23], and chemopreventive effects [24,25]. Our previous publication indicated that 6-MITC and its derivatives may have an inhibitory effect against pancreatic cancer cell growth (including cancer stem cells phenotype) [26].…”