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Curcumin induces FasL-related apoptosis through p38 activation in human hepatocellular carcinoma Huh7 cells.
- Source :
-
Life sciences [Life Sci] 2013 Mar 14; Vol. 92 (6-7), pp. 352-8. Date of Electronic Publication: 2013 Jan 24. - Publication Year :
- 2013
-
Abstract
- Aim: The aim of this study is to explore the underlying molecular mechanism of curcumin-induced apoptosis in human hepatocellular carcinoma (HCC) Huh7 cells.<br />Main Methods: Fas and FasL mRNA expression was analyzed by reverse transcription PCR. Western blot was applied to detect the protein expression of Bcl-2 family members, MAPK family members, c-Jun, c-Fos, ATF-2, caspase-3, PARP, TNF receptor family members and the respective ligands. Apoptotic cells were assayed with annexin V/PI double staining and flow cytometry.<br />Key Findings: Curcumin treatment resulted in a fast and significant increase of Fas and Fas ligand (FasL) along with activation of caspase-3 and cleavage of PARP in Huh7 cells. Inhibition of caspase-3 activity by the specific inhibitor Z-DEVD-FMK rescued Huh7 cells from curcumin-induced apoptosis. Neutralization of FasL significantly protected the cells from curcumin-induced caspase-3 activation and apoptosis in a dose-dependent manner. Moreover, p38 was rapidly activated in response to curcumin, and inactivation of p38 by pharmacologic inhibitor SB203580 dramatically suppressed curcumin-induced FasL expression and apoptosis.<br />Significance: Our results demonstrated that curcumin induces apoptosis through p38-denpendent up-regulation of FasL in Huh7 cells.<br /> (Copyright © 2012 Elsevier Inc. All rights reserved.)
- Subjects :
- Carcinoma, Hepatocellular pathology
Caspase 3 biosynthesis
Caspase Inhibitors pharmacology
Cell Line, Tumor
Humans
Imidazoles pharmacology
Oligopeptides pharmacology
Phosphorylation drug effects
Pyridines pharmacology
Signal Transduction drug effects
Up-Regulation drug effects
p38 Mitogen-Activated Protein Kinases antagonists & inhibitors
Apoptosis drug effects
Curcumin pharmacology
Fas Ligand Protein biosynthesis
fas Receptor biosynthesis
p38 Mitogen-Activated Protein Kinases metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1879-0631
- Volume :
- 92
- Issue :
- 6-7
- Database :
- MEDLINE
- Journal :
- Life sciences
- Publication Type :
- Academic Journal
- Accession number :
- 23352975
- Full Text :
- https://doi.org/10.1016/j.lfs.2013.01.013