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

Abstract

6-(Methylsulfinyl)hexyl isothiocyanate (6-MSITC), a major bioactive compound in Wasabi [Wasabia japonica (Miq.) Matsum.], has revealed the inhibitory effect on colon carcinogenesis in rat cancer model although the underlying mechanism is unclear. In this study, we used two types of human colorectal cancer cells (HCT116 p53 and HCT116 p53 ) to investigate the anticancer activity and molecular mechanisms of 6-MSITC. Interestingly, 6-MSITC inhibited the cell proliferation in both types of cells with similar IC value although a light increase in the phosphorylation and accumulation of P53 protein was observed in HCT116 p53 cells at 24 h after treatment. In addition, 6-MSITC increased the ratio of proapoptotic cells in both types of cells with the same fashion in a p53-independent manner. The data from mitochondrial analysis revealed that 6-MSITC enhanced the ratio of proapoptotic B-cell lymphoma-2-associated X protein/antiapoptotic myeloid cell leukemia 1, and sequentially caused mitochondrial membrane potential (ΔΨ ) loss, cytochrome c release, and caspase-3 activation in both types of cells. Taken together, Wasabi 6-MSITC induced apoptosis of human colorectal cancer cells in p53-independent mitochondrial dysfunction pathway. These findings suggest that 6-MSITC might be a potential agent for colon cancer chemoprevention although with p53 mutation. © 2018 BioFactors, 2018.

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

“…The mode of cell death was through two distinct pathways involving autophagy and mitotic arrest. It has been reported that 6-MITC possesses antitumor characteristics through the inhibition of nuclear factor-kappaB (NF-κB) pathway, the disturbance of mitochondrial function, and finally, the induction of cell apoptosis in different cancer cells [27,28]. Previously, we found that 6-MITC acted against tumor cell growth through mitotic arrest, the induction of apoptosis, and the inhibition of the expression of SOX2, a cancer stem cell molecule in human pancreatic cancer cells [26].…”

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 ]. During the cell cycle, the G2/M phase is more sensitive to radiation than other cell cycle phases and more sensitive in the mitotic phase compared to the G2 phase.…”

Microwave-Assisted versus Conventional Isolation of Glucosinolate Degradation Products from Lunaria annua L. and Their Cytotoxic Activity

“…Further investigation of the neuroprotective effect on IMR-32 human neuroblastoma cells was conducted by Trio et al, who concluded that 6-(methylsulfinyl)hexyl ITC can exert a neuroprotective effect by activating the Nrf2-mediated oxidative stress response pathway [27]. Likewise, 6-(methylsulfinyl)hexyl ITC showed inhibitory effect on colon carcinogenesis through a p53-independent mitochondrial dysfunction pathway [28]. Inhibition of viability, accompanied by the features of mitotic arrest and apoptosis of human pancreatic cancer cell lines PANC-1 and BxPC-3 were also observed for 6-(methylsulfinyl)hexyl ITC [29].…”