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NF-kappa B modulation is involved in celastrol induced human multiple myeloma cell apoptosis.
- Source :
-
PloS one [PLoS One] 2014 Apr 22; Vol. 9 (4), pp. e95846. Date of Electronic Publication: 2014 Apr 22 (Print Publication: 2014). - Publication Year :
- 2014
-
Abstract
- Celastrol is an active compound extracted from the root bark of the traditional Chinese medicine Tripterygium wilfordii Hook F. To investigate the effect of celastrol on human multiple myeloma cell cycle arrest and apoptosis and explore its molecular mechanism of action. The activity of celastrol on LP-1 cell proliferation was detected by WST-8 assay. The celastrol-induced cell cycle arrest was analyzed by flow cytometry after propidium iodide staining. Nuclear translocation of the nuclear factor kappa B (NF-κB) was observed by fluorescence microscope. Celastrol inhibited cell proliferation of LP-1 myeloma cell in a dose-dependent manner with IC50 values of 0.8817 µM, which was mediated through G1 cell cycle arrest and p27 induction. Celastrol induced apoptosis in LP-1 and RPMI 8226 myeloma cells in a time and dose dependent manner, and it involved Caspase-3 activation and NF-κB pathway. Celastrol down-modulated antiapoptotic proteins including Bcl-2 and survivin expression. The expression of NF-κB and IKKa were decreased after celastrol treatment. Celastrol effectively blocked the nuclear translocation of the p65 subunit and induced human multiple myeloma cell cycle arrest and apoptosis by p27 upregulation and NF-kB modulation. It has been demonstrated that the effect of celastrol on NF-kB was HO-1-independent by using zinc protoporphyrin-9 (ZnPPIX), a selective heme oxygenase inhibitor. From the results, it could be inferred that celastrol may be used as a NF-kB inhibitor to inhibit myeloma cell proliferation.
- Subjects :
- Active Transport, Cell Nucleus drug effects
Caspase 3 metabolism
Cell Line, Tumor drug effects
Cell Proliferation drug effects
Cell Survival drug effects
Cyclin-Dependent Kinase Inhibitor p27 metabolism
Drug Screening Assays, Antitumor
G1 Phase Cell Cycle Checkpoints drug effects
Humans
I-kappa B Proteins metabolism
Inhibitory Concentration 50
NF-KappaB Inhibitor alpha
Pentacyclic Triterpenes
Transcription Factor RelA antagonists & inhibitors
Antineoplastic Agents pharmacology
Apoptosis drug effects
Multiple Myeloma drug therapy
Transcription Factor RelA metabolism
Triterpenes pharmacology
Subjects
Details
- Language :
- English
- ISSN :
- 1932-6203
- Volume :
- 9
- Issue :
- 4
- Database :
- MEDLINE
- Journal :
- PloS one
- Publication Type :
- Academic Journal
- Accession number :
- 24755677
- Full Text :
- https://doi.org/10.1371/journal.pone.0095846