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Open AccessArticle

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

by Kun-Ming Wu 1,2,3, Hui-Fen Liao 4, Chih-Wen Chi 5,6, Yu Ru Kou 1,* and Yu-Jen Chen 3,5,7,8,*
1
Institute of Physiology, School of Medicine, National Yang-Ming University, Taipei 11221, Taiwan
2
Chest Division, Department of Internal Medicine, MacKay Memorial Hospital, Taipei 10449, Taiwan
3
Mackay Junior College of Medicine, Nursing, and Management, Taipei 25245, Taiwan
4
Department of Biochemical Science and Technology, National Chiayi University, Chiayi 60004, Taiwan
5
Department of Medical Research, MacKay Memorial Hospital, New Taipei City 25160, Taiwan
6
Department of Nursing, MacKay Medical College, New Taipei City 25245, Taiwan
7
Department of Medical Research, China Medical University Hospital, Taichung 40402, Taiwan
8
Department of Radiation Oncology, MacKay Memorial Hospital, Taipei 10449, Taiwan
*
Authors to whom correspondence should be addressed.
Biomolecules 2019, 9(12), 774; https://doi.org/10.3390/biom9120774
Received: 10 September 2019 / Revised: 15 November 2019 / Accepted: 18 November 2019 / Published: 23 November 2019
A natural compound from Wasabia japonica, 6-(methylsulfinyl) hexyl isothiocyanate (6-MITC) was investigated for its anti-leukemia activity and mechanism of action. It was found that 6-MITC inhibited the viability of human chronic myelogenous leukemia K562 cells along with extensive mitotic arrest, spindle multipolarity, and cytoplasmic vacuole accumulation. The evidence of autophagy included the validation of autophagosomes with double-layered membranes under transmission electron microscopy, LC3I/II conversion, and the induction of G2/M phase arrest observed with acridine orange staining of treated cells, as well as the elevation of phosphorylated-histone H3 expression at the M phase. With regard to the expression of proteins related to mitosis, the downregulation of p-CHK1, p-CHK2, p-cdc25c, and p-cdc2, as well as the upregulation of cyclin B1, p-cdc20, cdc23, BubR1, Mad2, and p-plk-1 was observed. The knockdown of cdc20 was unable to block the effect of 6-MITC. The differentiation of k562 cells into monocytes, granulocytes, and megakaryocytes was not affected by 6-MITC. The 6-MITC-induced unique mode of cell death through the concurrent induction of mitosis and autophagy may have therapeutic potential. Further studies are required to elucidate the pathways associated with the counteracting occurrence of mitosis and autophagy.
Keywords: wasabi; 6-(methylsulfinyl) hexyl isothiocyanate; mitosis; autophagy; chronic myelogenous leukemia wasabi; 6-(methylsulfinyl) hexyl isothiocyanate; mitosis; autophagy; chronic myelogenous leukemia
MDPI and ACS Style

Wu, K.-M.; Liao, H.-F.; Chi, C.-W.; Kou, Y.R.; Chen, Y.-J. Wasabi Compound 6-(Methylsulfinyl) Hexyl Isothiocyanate Induces Cell Death with Coexisting Mitotic Arrest and Autophagy in Human Chronic Myelogenous Leukemia K562 Cells. Biomolecules 2019, 9, 774.

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