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Recombinant Multivalent EMMPRIN Extracellular Domain Induces U937 Human Leukemia Cell Apoptosis by Downregulation of Monocarboxylate Transporter 1 and Activation of Procaspase-9

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Abstract

This study was carried out to understand the effect of the recombinant multivalent extracellular matrix metalloproteinase inducer (EMMPRIN) extracellular domain, designated as rmEMMPRINex, on the apoptotic cell death of human leukemia U937 cells. Expression of monocarboxylate transporter 1 (MCT1) and caspase-9 in U937 treated with rmEMMPRINex was investigated in this study. Levels of membrane MCT1 and intracellular procaspase-9 were decreased in rmEMMPRINex-treated cells in comparison to controls. However, the expression of activated caspase-9 was undetectable. rmEMMPRINex also induced DNA fragmentation and apoptosis in U937 cells. Taken together, we concluded that interaction of rmEMMPRINex with U937 cells leads to inhibition of MCT1 membrane expression, intracellular activation of procaspase-9, followed by DNA fragmentation and apoptosis. This may contribute to the conceptual development of novel cancer drugs in the future.

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Acknowledgments

This work was supported by the Thailand Research Fund, the Commission on Higher Education, Chiang Mai University and the NSTDA Research Chair Grant, National Sciences and Technology Development Agency (Thailand). The author is eternally grateful to Mr. Wutigri Nimlamool, Ms. Watinee Yatfoong, Mr. Somphot Saoin, Mr. Prakitnavin Pingmuang, Mr. Chatree Plianpairoj, Ms. Patcharee Nochod, Ms. Kamonrat Puttimool, Mr. Warachai Praditwongwarn, Ms. Tipattaraporn Panich, and Mr. Anucha Pikool for their technical assistances. We also acknowledge Mr. Landon Wark for English proofing.

Conflict of interest

We declare that we have no conflict of interest.

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Authors and Affiliations

  1. Division of Clinical Microscopy, Department of Medical Technology, Faculty of Associated Medical Sciences, Chiang Mai University, 110 Intawaroros Road, Sripoom, Muang, Chiang Mai, 50200, Thailand

    Nutjeera Intasai

  2. Biomedical Technology Research Unit, National Center for Genetic Engineering and Biotechnology, National Science and Technology Development Agency at the Faculty of Associated Medical Sciences, Chiang Mai University, 110 Intawaroros Road, Sripoom, Muang, Chiang Mai, 50200, Thailand

    Nutjeera Intasai, Supansa Pata, Khajornsak Tragoolpua & Chatchai Tayapiwatana

  3. Division of Clinical Immunology, Department of Medical Technology, Faculty of Associated Medical Sciences, Chiang Mai University, 110 Intawaroros Road, Sripoom, Muang, Chiang Mai, 50200, Thailand

    Supansa Pata & Chatchai Tayapiwatana

  4. Division of Clinical Microbiology, Department of Medical Technology, Faculty of Associated Medical Sciences, Chiang Mai University, 110 Intawaroros Road, Sripoom, Muang, Chiang Mai, 50200, Thailand

    Khajornsak Tragoolpua

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  1. Nutjeera Intasai
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Correspondence to Nutjeera Intasai.

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Intasai, N., Pata, S., Tragoolpua, K. et al. Recombinant Multivalent EMMPRIN Extracellular Domain Induces U937 Human Leukemia Cell Apoptosis by Downregulation of Monocarboxylate Transporter 1 and Activation of Procaspase-9. Appl Biochem Biotechnol 176, 1781–1790 (2015). https://doi.org/10.1007/s12010-015-1677-0

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