| 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. | |
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MedLine Citation:
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PMID: 20472557 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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. |
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Authors:
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Sunil K Manna; Julie S Bose; Vijay Gangan; Nune Raviprakash; Thota Navaneetha; Pongali B Raghavendra; Banaganapalli Babajan; Chitta S Kumar; Swatantra K Jain |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2010-05-14 |
Journal Detail:
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Title: The Journal of biological chemistry Volume: 285 ISSN: 1083-351X ISO Abbreviation: J. Biol. Chem. Publication Date: 2010 Jul |
Date Detail:
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Created Date: 2010-07-12 Completed Date: 2010-08-06 Revised Date: 2011-08-01 |
Medline Journal Info:
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Nlm Unique ID: 2985121R Medline TA: J Biol Chem Country: United States |
Other Details:
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Languages: eng Pagination: 22318-27 Citation Subset: IM |
Affiliation:
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Laboratory of Immunology, Centre for DNA Fingerprinting and Diagnostics, Nampally, Hyderabad 500 001, India. manna@cdfd.org.in |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Benzofurans
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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:
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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 | |
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