Document Detail


Resveratrol downregulates the constitutional activation of nuclear factor-kappaB in multiple myeloma cells, leading to suppression of proliferation and invasion, arrest of cell cycle, and induction of apoptosis.
MedLine Citation:
PMID:  16490592     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Resveratrol has been proposed to act as a chemopreventive agent in numerous epidemiologic studies and has been shown to inhibit proliferation of various tumor cells in vitro. In the present study, we investigated the antitumor effects of resveratrol on multiple myeloma (MM) cells and the mechanisms involved. Our findings indicated that resveratrol inhibited proliferation of tumor cells in a dose- [corrected] dependent manner by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and [3H]thymidine incorporation assay. Resveratrol also enhanced the inhibitory effect of dexamethasone on the growth of MM cells by MTT assay. Flow cytometric analysis demonstrated that resveratrol arrested the cells at the G1 and S phases of the cell cycle. Because nuclear factor-kappaB (NF-kappaB) plays a key role in cell survival and proliferation of human MM cells, we tested the effect of resveratrol on NF-kappaB expression by Western blot analysis and immunofluorescence. NF-kappaB was constitutively active in all human MM cell lines examined, and resveratrol down-regulated NF-kappaB expression in all cell lines. Resveratrol also down-regulated the expression of NF-kappaB-regulated gene products by Western blot analysis, gelatin zymography, and enzyme-linked immunosorbent assay, including interleukin-6, Bcl-2, Bcl-xL, XIAP, c-IAP, vascular endothelial growth factor (VEGF), and matrix metalloproteinase-9 (MMP-9), which modulates an array of signals controlling cellular survival and proliferation and tumor promotion. Indeed, annexin V-fluoroisothyocyanate and Transwell invasion analyses revealed that incubation of MM cells with resveratrol resulted in apoptotic cell death and inhibition of invasion. In conclusion, these data suggest that resveratrol is an effective in vitro inhibitor of NF-kappaB in human MM cells. Resveratrol plays a role in suppressing the proliferation of MM cells and induces apoptosis, thus providing the molecular basis for the treatment of MM patients with this compound.
Authors:
Chunyan Sun; Yu Hu; Xinyue Liu; Tao Wu; Yadan Wang; Wenjuan He; Wenning Wei
Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Cancer genetics and cytogenetics     Volume:  165     ISSN:  0165-4608     ISO Abbreviation:  Cancer Genet. Cytogenet.     Publication Date:  2006 Feb 
Date Detail:
Created Date:  2006-02-21     Completed Date:  2006-05-16     Revised Date:  2013-06-03    
Medline Journal Info:
Nlm Unique ID:  7909240     Medline TA:  Cancer Genet Cytogenet     Country:  United States    
Other Details:
Languages:  eng     Pagination:  9-19     Citation Subset:  IM    
Affiliation:
Institute of Hematology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, PR China.
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MeSH Terms
Descriptor/Qualifier:
Apoptosis / drug effects*
Cell Cycle / drug effects*
Cell Division / drug effects*
Cell Line, Tumor
Cell Nucleus / drug effects,  pathology
DNA Replication / drug effects*
Humans
Multiple Myeloma / genetics*,  pathology
NF-kappa B / genetics*
Neoplasm Invasiveness / prevention & control
Stilbenes / pharmacology*
Chemical
Reg. No./Substance:
0/NF-kappa B; 0/Stilbenes; Q369O8926L/resveratrol
Comments/Corrections
Erratum In:
Cancer Genet Cytogenet. 2006 Nov;171(1):81

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