|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.|
|PMID: 20472557 Owner: NLM Status: MEDLINE|
|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.|
|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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|Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2010-05-14|
|Title: The Journal of biological chemistry Volume: 285 ISSN: 1083-351X ISO Abbreviation: J. Biol. Chem. Publication Date: 2010 Jul|
|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|
|Languages: eng Pagination: 22318-27 Citation Subset: IM|
|Laboratory of Immunology, Centre for DNA Fingerprinting and Diagnostics, Nampally, Hyderabad 500 001, India. firstname.lastname@example.org|
|APA/MLA Format Download EndNote Download BibTex|
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*
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
|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 126.96.36.199/Poly(ADP-ribose) Polymerases; EC 3.4.22.-/Caspases; EC 188.8.131.52/MDM2 protein, human; EC 184.108.40.206/Proto-Oncogene Proteins c-mdm2|
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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