PKC and MEK pathways inhibit caspase-9/-3-mediated cytotoxicity in differentiated cells

Yiang, Giou-Teng; Yu, Yung-Luen; Hu, Sheng-Chuan; Chen, Mark Hung-Chih; Wang, Jaang-Jiun; Wei, Chyou-Wei

doi:10.1016/j.febslet.2008.02.018

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Volume 582, Issue 6 , Pages 881-885, 19 March 2008

PKC and MEK pathways inhibit caspase-9/-3-mediated cytotoxicity in differentiated cells

Edited by Lukas Huber

Giou-Teng Yiang
- Institute of Medical Sciences, Tzu-Chi University, Hualien, Taiwan
- Department of Emergency Medicine, Tzu-Chi General Hospital, Hualien, Taiwan
- These authors contributed equally to this work.
Yung-Luen Yu
- Graduate Institute of Cancer Biology, China Medical University, Taichung, Taiwan
- Center for Molecular Medicine, China Medical University Hospital, Taichung, Taiwan
- Department of Biotechnology, Asia University, Taichung, Taiwan
- These authors contributed equally to this work.
Sheng-Chuan Hu
- Institute of Medical Sciences, Tzu-Chi University, Hualien, Taiwan
- Department of Emergency Medicine, Tzu-Chi General Hospital, Hualien, Taiwan
- These authors contributed equally to this work.
Mark Hung-Chih Chen
- Institute of Clinical Nutrition, College of Medicines and Nursings, Hungkuang University, No. 34, Chung-Chie Road, Sha Lu, Taichung 433, Taiwan, ROC
- Department of Biotechnology, Hungkuang University, Sha Lu, Taichung, Taiwan
Jaang-Jiun Wang
- Division of Pediatric Infectious Diseases, Emory University School of Medicine, Atlanta, USA
- This author is co-correspondence author to this study.
Chyou-Wei Wei
- Institute of Clinical Nutrition, College of Medicines and Nursings, Hungkuang University, No. 34, Chung-Chie Road, Sha Lu, Taichung 433, Taiwan, ROC
- Corresponding author. Fax: +886 4 26338212.

Received 8 January 2008; received in revised form 31 January 2008; accepted 6 February 2008. published online 18 February 2008.

Abstract

Many studies have indicated that differentiated cells inhibit drug-induced cytotoxicity but undifferentiated cells do not, though the mechanisms are unclear. Currently, HL-60 cells are induced to differentiate into macrophage-like cells with Phorbol-12-myristate-13-acetate (TPA) treatment (TPA-differentiated cells). Our study shows that caspase-9/-3-mediated cytotoxicity can be induced in undifferentiated HL-60 cells but not in TPA-differentiated HL-60 cells. However, caspase-9/-3-mediated cytotoxicity can be induced in TPA-differentiated cells if they are pretreated with a protein kinase C (PKC) or a mitogen activated protein kinase (MEK) inhibitor. Taken together, this study demonstrates that TPA-differentiated HL-60 cells inhibit caspases-9/-3-mediated cytotoxicity through the PKC and MEK signaling pathways.

Keywords: Caspases, PKC, MEK, Differentiation