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http://dx.doi.org/10.4196/kipp.2011.15.1.1

Involvement of ROS in Curcumin-induced Autophagic Cell Death  

Lee, Youn-Ju (Department of Pharmacology, College of Medicine, Catholic University of Daegu)
Kim, Nam-Yi (Department of Biochemistry and Molecular Biology, School of Medicine, Yeungnam University)
Suh, Young-Ah (Institute for Innovative Cancer Research, Asan Medical Center)
Lee, Chu-Hee (Department of Biochemistry and Molecular Biology, School of Medicine, Yeungnam University)
Publication Information
The Korean Journal of Physiology and Pharmacology / v.15, no.1, 2011 , pp. 1-7 More about this Journal
Abstract
Many anticancer agents as well as ionizing radiation have been shown to induce autophagy which is originally described as a protein recycling process and recently reported to play a crucial role in various disorders. In HCT116 human colon cancer cells, we found that curcumin, a polyphenolic phytochemical extracted from the plant Curcuma longa, markedly induced the conversion of microtubule-associated protein 1 light chain 3 (LC3)-I to LC3-II and degradation of sequestome-1 (SQSTM1) which is a marker of autophagosome degradation. Moreover, we found that curcumin caused GFP-LC3 formation puncta, a marker of autophagosome, and decrease of GFP-LC3 and SQSTM1 protein level in GFP-LC3 expressing HCT116 cells. It was further confirmed that treatment of cells with hydrogen peroxide induced increase of LC3 conversion and decrease of GFP-LC3 and SQSTM1 levels, but these changes by curcumin were almost completely blocked in the presence of antioxidant, N-acetylcystein (NAC), indicating that curcumin leads to reactive oxygen species (ROS) production, which results in autophagosome development and autolysosomal degradation. In parallel with NAC, SQSTM1 degradation was also diminished by bafilomycin A, a potent inhibitor of autophagosome-lysosome fusion, and cell viability assay was further confirmed that cucurmin-induced cell death was partially blocked by bafilomycin A as well as NAC. We also observed that NAC abolished curcumin-induced activation of extracelluar signal-regulated kinases (ERK) 112 and p38 mitogen-activated protein kinases (MAPK), but not Jun N-terminal kinase (JNK). However, the activation of ERK1/2 and p38 MAPK seemed to have no effect on the curcumin-induced autophagy, since both the conversion of LC3 protein and SQSTM1 degradation by curcumin was not changed in the presence of NAC. Taken together, our data suggest that curcumin induced ROS production, which resulted in autophagic activation and concomitant cell death in HCT116 human colon cancer cell. However, ROS-dependent activation of ERK1/2 and p38 MAPK, but not JNK, might not be involved in the curcumin-induced autophagy.
Keywords
Autophagy; Curcumin; Microtubule-associated protein 1 light chain 3; Mitogen-activated protein kinase; Sequestome-1; Reactive oxygen species;
Citations & Related Records
Times Cited By KSCI : 1  (Citation Analysis)
Times Cited By Web Of Science : 14  (Related Records In Web of Science)
Times Cited By SCOPUS : 4
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