alexa Cytotoxicity and Apoptogenic Activity of A Novel Synthetic Iron Chelator 1-(N-Acetyl-6-Aminohexyl)-3-Hydroxy-2-Methylpyridin-4-One (CM1) In Human Leukemic Cells
ISSN: 2376-1318

Vitamins & Minerals
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Research Article

Cytotoxicity and Apoptogenic Activity of A Novel Synthetic Iron Chelator 1-(N-Acetyl-6-Aminohexyl)-3-Hydroxy-2-Methylpyridin-4-One (CM1) In Human Leukemic Cells

Nittaya Chansiw1, Kanjana Pangjit1,2, Wirote Tuntiwechapikul1, Chada Phisalaphong3, Suthat Fucharoen4, John B. Porter5 and Somdet Srichairatanakool1*
1Department of Biochemistry, Faculty of Medicine, Chiang Mai University, Thailand
2College of Medicine and Public Health, Ubon Ratchathani University, Thailand
3Institute of Research and Development, Government Pharmaceutical Organization, Ministry of Public Health, Thailand
4Thalassemia Research Center, Institute of Molecular Bioscience, Mahidol University Salaya Campus, Thailand
5Department of Haematology, UCL Cancer Institute, University College London, Hunley Street, United Kingdom
Corresponding Author : Somdet Srichairatanakool
Department of Biochemistry, Faculty of Medicine
Chiang Mai University, Thailand
E-mail: [email protected]
Received July 02, 2013; Accepted July 04, 2013; Published July 30, 2013
Citation: Chansiw N, Pangjit K, Tuntiwechapikul W, Phisalaphong C, Fucharoen S, et al. (2013) Cytotoxicity and Apoptogenic Activity of A Novel Synthetic Iron Chelator 1-(N-Acetyl-6-Aminohexyl)-3-Hydroxy-2-Methylpyridin-4-One (CM1) In Human Leukemic Cells. Vitam Miner 2:114. doi:10.4172/vms.1000114
Copyright: © 2013 Chansiw N, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
 

Abstract

An interruption of the iron metabolism with chelators can lead to a significant inhibition of cancer cell growth. 1-(N-acetyl-6-aminohexyl)-3-hydroxy-2-methylpyridin-4-one or CM1, is a novel synthetic bidentate iron chelator which was successfully synthesized by our group. We have studied the characteristics and iron-chelating activity of this compound. Nevertheless, the anti-cancer activity of the chelator is largely unknown. In this study, we demonstrated the cytotoxicity and apoptogenic activity of CM1 against human leukemic cell lines-HL-60 and U937. 3-(4,5-Dimethylthiazol- 2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay was performed for the cytotoxicity study. The results showed that CM1 inhibited the cell growth and metabolic activity of the leukemic cells. Flow cytometric analysis clearly demonstrated the dose and time-response of CM1-induced apoptosis in these two cells. CM1 arrested the cell populations in the sub G1 phase after 24 hours of exposure. The cancer cells induced by the compound significantly decreased mitochondria membrane potential (Δψm), and increased the activation of caspase-2,-3,-8 and caspase-9 activities. Possibly, CM1 would interact with nonheme iron-containing enzymes, such as ribonucleotide reductase and depleting intracellular iron essential for fast dividing cancer cells, leading to cell apoptosis. The CM1 may act as a reducing agent and help to maintain the CM1-Fe2+ complex which can generate radicals.

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