PMID- 21461234
OWN - NLM
STAT- PubMed-not-MEDLINE
DCOM- 20110714
LR  - 20211020
IS  - 2093-3827 (Electronic)
IS  - 1226-4512 (Print)
IS  - 1226-4512 (Linking)
VI  - 15
IP  - 1
DP  - 2011 Feb
TI  - Involvement of ROS in Curcumin-induced Autophagic Cell Death.
PG  - 1-7
LID - 10.4196/kjpp.2011.15.1.1 [doi]
AB  - 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) 1/2 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.
FAU - Lee, Youn Ju
AU  - Lee YJ
AD  - Department of Pharmacology, College of Medicine, Catholic University of Daegu, 
      Daegu 705-718, Korea.
FAU - Kim, Nam-Yi
AU  - Kim NY
FAU - Suh, Young-Ah
AU  - Suh YA
FAU - Lee, Chuhee
AU  - Lee C
LA  - eng
PT  - Journal Article
DEP - 20110228
PL  - Korea (South)
TA  - Korean J Physiol Pharmacol
JT  - The Korean journal of physiology & pharmacology : official journal of the Korean 
      Physiological Society and the Korean Society of Pharmacology
JID - 9709505
PMC - PMC3062078
OTO - NOTNLM
OT  - Autophagy
OT  - Curcumin
OT  - Microtubule-associated protein 1 light chain 3
OT  - Mitogen-activated protein kinase
OT  - Reactive oxygen species
OT  - Sequestome-1
EDAT- 2011/04/05 06:00
MHDA- 2011/04/05 06:01
PMCR- 2011/02/01
CRDT- 2011/04/05 06:00
PHST- 2010/10/11 00:00 [received]
PHST- 2011/02/07 00:00 [revised]
PHST- 2011/02/07 00:00 [accepted]
PHST- 2011/04/05 06:00 [entrez]
PHST- 2011/04/05 06:00 [pubmed]
PHST- 2011/04/05 06:01 [medline]
PHST- 2011/02/01 00:00 [pmc-release]
AID - 10.4196/kjpp.2011.15.1.1 [doi]
PST - ppublish
SO  - Korean J Physiol Pharmacol. 2011 Feb;15(1):1-7. doi: 10.4196/kjpp.2011.15.1.1. 
      Epub 2011 Feb 28.