Document Detail


Novel derivative of benzofuran induces cell death mostly by G2/M cell cycle arrest through p53-dependent pathway but partially by inhibition of NF-kappaB.
MedLine Citation:
PMID:  20472557     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The Dracaena resin is widely used in traditional medicine as an anticancer agent, and benzofuran lignan is the active component. In this report, we provide evidence that the synthetic derivative of benzofuran lignan (Benfur) showed antitumor activities. It induced apoptosis in p53-positive cells. Though it inhibited endotoxin-induced nuclear factor kappaB (NF-kappaB) activation in both p53-positive and -negative cells, the activation of caspase 3 was observed in p53-positive cells. It showed partial cell death effect in both p53-positive and -negative cells through inhibition of NF-kappaB. Cell cycle analysis using flow cytometry showed that treatment with this novel benozofuran lignan derivative to Jurkat T-cells, but not U-937 cells, resulted in a G2/M arrest in a dose- and time-dependent manner. It increased amounts of p21, p27, and cyclin B, but not phospho-Rb through p53 nuclear translocation in Jurkat T-cells, but not in U-937 cells. It inhibited amounts of MDM2 (murine double minute 2) by repressing the transcription factor Sp1, which was also proved in silico. It induced cell death in tumor cells, but not in primary T-cells. Overall, our data suggest that Benfur-mediated cell death is partially dependent upon NF-kappaB, but predominantly dependent on p53. Thus, this novel benzofuran lignan derivative can be effective chemopreventive or chemotherapeutic agent against malignant T-cells.
Authors:
Sunil K Manna; Julie S Bose; Vijay Gangan; Nune Raviprakash; Thota Navaneetha; Pongali B Raghavendra; Banaganapalli Babajan; Chitta S Kumar; Swatantra K Jain
Related Documents :
7989317 - Suspension-mediated induction of hepa 1c1c7 cyp1a-1 expression is dependent on the ah r...
9393737 - Intracellular localization of p53 tumor suppressor protein in gamma-irradiated cells is...
10554637 - Radiochemotherapy with paclitaxel: synchronization effects and the role of p53.
8453637 - P53 mutations selected in vivo when mouse mammary epithelial cells form hyperplastic ou...
22987627 - Early gonadogenesis in mammals: significance of long and narrow gonadal structure.
8706017 - Brain-derived neurotrophic factor protects neuroblastoma cells from vinblastine toxicity.
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2010-05-14
Journal Detail:
Title:  The Journal of biological chemistry     Volume:  285     ISSN:  1083-351X     ISO Abbreviation:  J. Biol. Chem.     Publication Date:  2010 Jul 
Date Detail:
Created Date:  2010-07-12     Completed Date:  2010-08-06     Revised Date:  2013-05-29    
Medline Journal Info:
Nlm Unique ID:  2985121R     Medline TA:  J Biol Chem     Country:  United States    
Other Details:
Languages:  eng     Pagination:  22318-27     Citation Subset:  IM    
Affiliation:
Laboratory of Immunology, Centre for DNA Fingerprinting and Diagnostics, Nampally, Hyderabad 500 001, India. manna@cdfd.org.in
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
Descriptor/Qualifier:
Benzofurans / pharmacology*
Caspases / metabolism
Cell Death / drug effects
Cell Line, Tumor
Cyclin-Dependent Kinase Inhibitor p21 / metabolism
Cyclin-Dependent Kinase Inhibitor p27 / metabolism
Cytochromes c / metabolism
Cytoplasm / drug effects,  metabolism
DNA, Neoplasm / metabolism
Drug Screening Assays, Antitumor
Enzyme Activation / drug effects
G2 Phase / drug effects*
Humans
I-kappa B Proteins / metabolism
Lignans / pharmacology*
Mitosis / drug effects*
NF-kappa B / antagonists & inhibitors*,  metabolism
Organ Specificity / drug effects
Poly(ADP-ribose) Polymerases / metabolism
Protein Binding / drug effects
Proto-Oncogene Proteins c-mdm2 / metabolism
Signal Transduction / drug effects*
Sp1 Transcription Factor / metabolism
Transcription Factor RelA / metabolism
Tumor Suppressor Protein p53 / metabolism*
bcl-2-Associated X Protein / metabolism
Chemical
Reg. No./Substance:
0/Benzofurans; 0/Cyclin-Dependent Kinase Inhibitor p21; 0/DNA, Neoplasm; 0/I-kappa B Proteins; 0/Lignans; 0/NF-kappa B; 0/Sp1 Transcription Factor; 0/Transcription Factor RelA; 0/Tumor Suppressor Protein p53; 0/bcl-2-Associated X Protein; 139874-52-5/NF-kappaB inhibitor alpha; 147604-94-2/Cyclin-Dependent Kinase Inhibitor p27; 9007-43-6/Cytochromes c; EC 2.4.2.30/Poly(ADP-ribose) Polymerases; EC 3.4.22.-/Caspases; EC 6.3.2.19/MDM2 protein, human; EC 6.3.2.19/Proto-Oncogene Proteins c-mdm2
Comments/Corrections

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


Previous Document:  Reduction of brain beta-amyloid (Abeta) by fluvastatin, a hydroxymethylglutaryl-CoA reductase inhibi...
Next Document:  Importance of protein-tyrosine phosphatase-alpha catalytic domains for interactions with SHP-2 and i...