IL-1beta Acts in Synergy with Endogenous IL-1beta in A375-S2 Human Melanoma Cell Apoptosis Through Mitochondrial Pathway.
10.3346/jkms.2005.20.4.555
- Author:
Che WANG
1
;
Min Wei WANG
;
Shin Ichi TASHIRO
;
Satoshi ONODERA
;
Takashi IKEJIMA
Author Information
1. China-Japan Research Institute of Medical and Pharmaceutical Sciences, Shenyang Pharmaceutical University, China. ikejimat@vip.sina.com
- Publication Type:Original Article ; Comparative Study
- Keywords:
Interleukin-1;
Human melanoma Cells;
Apoptosis;
Caspases;
Mitochondria
- MeSH:
Apoptosis/*drug effects;
Blotting, Western;
Caspase 1/metabolism;
Caspases/metabolism;
Cell Line, Tumor;
Cell Proliferation/drug effects;
Cell Survival/drug effects;
Comparative Study;
DNA Fragmentation/drug effects;
Deoxyribonucleases/metabolism;
Dose-Response Relationship, Drug;
Enzyme Activation/drug effects;
Humans;
Interleukin-1/biosynthesis/*pharmacology/physiology;
Interleukin-6/pharmacology;
Lymphotoxin/pharmacology;
Melanoma/metabolism/pathology/physiopathology;
Mitochondria/*physiology;
Poly(ADP-ribose) Polymerases/metabolism;
Proto-Oncogene Proteins c-bcl-2/biosynthesis;
Time Factors
- From:Journal of Korean Medical Science
2005;20(4):555-561
- CountryRepublic of Korea
- Language:English
-
Abstract:
Interleukin-1beta (IL-1beta) is a pivotal proinflammatory cytokine. To investigate the mechanism of IL-1beta-induced cell death in human malignant melanoma A375-S2 cells, MTT assay, photomicroscopical observation, DNA agarose gel electrophoresis, radioimmunoassay and Western blot analysis were carried out. IL-1beta did not only induce nuclear condensation and DNA fragmentation, but also increased degradation of two substrates of caspase-3, poly ADP-ribose polymerase (PARP) and inhibitor of caspase-activated DNase (ICAD). Simultaneously, release of precursor of IL-1beta (pro-IL-1beta) and endogenous IL-1beta production were involved in the apoptotic process. IL-1beta enhanced the ratio of Bax/Bcl-2 and Bax/Bcl-xL expression and up-regulated apoptosis inducing factor (AIF) expression, which required the activation of downstream caspases. These results suggest that IL-1beta induces endogenous IL-1beta production, enhances cleavage of caspase downstream substrates and promotes mitochondria mediated apoptosis in A375-S2 cells.
