Document Detail


Plumbagin induces cell death through a copper-redox cycle mechanism in human cancer cells.
MedLine Citation:
PMID:  19505895     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Plumbagin, a naphthoquinone derived from the medicinal plant Plumbago zeylanica has been shown to exert anticancer and anti-proliferative activities in cells in culture as well as animal tumor models. In our previous paper, we have reported the cytotoxic action of plumbagin in plasmid pBR322 DNA as well as human peripheral blood lymphocytes through a redox mechanism involving copper. Copper has been shown to be capable of mediating the action of several plant-derived compounds through production of reactive oxygen species (ROS). The objective of the present study was to determine whether plumbagin induces apoptosis in human cancer cells through the same mechanism which we proposed earlier. Using 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium, inner salt assay, 3-(4,5-B-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay for cell growth inhibition, histone/DNA ELISA, homogeneous caspase-3/7 assay for apoptosis as well as alkaline comet assay for DNA single-strand breaks detection in this report, we confirm that plumbagin causes effective cell growth inhibition, induces apoptosis and generates single-strand breaks in cancer cells. Incubation of cancer cells with scavengers of ROS and neocuproine inhibited the cytotoxic action of plumbagin proving that generation of ROS and Cu(I) are the critical mediators in plumbagin-induced cell growth inhibition. This study is the first to investigate the copper-mediated anticancer mechanism of plumbagin in human cancer cells and these properties of plumbagin could be further explored for the development of anticancer agents with higher therapeutic indices, especially for skin cancer.
Authors:
S Nazeem; Asfar S Azmi; Sarmad Hanif; Aamir Ahmad; Ramzi M Mohammad; S M Hadi; K Sateesh Kumar
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Publication Detail:
Type:  Journal Article     Date:  2009-06-07
Journal Detail:
Title:  Mutagenesis     Volume:  24     ISSN:  1464-3804     ISO Abbreviation:  Mutagenesis     Publication Date:  2009 Sep 
Date Detail:
Created Date:  2009-08-31     Completed Date:  2009-12-30     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8707812     Medline TA:  Mutagenesis     Country:  England    
Other Details:
Languages:  eng     Pagination:  413-8     Citation Subset:  IM    
Affiliation:
Department of Biochemistry, Faculty of Life Sciences, Aligarh Muslim University, Aligarh 202002, Uttar Pradesh, India.
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MeSH Terms
Descriptor/Qualifier:
Cell Death / drug effects
Cell Line, Tumor
Cell Nucleus / drug effects,  metabolism
Cell Proliferation / drug effects
Cell Shape / drug effects
Comet Assay
Copper / metabolism*,  pharmacology
Cytoprotection / drug effects
Free Radical Scavengers / pharmacology
Humans
Naphthoquinones / pharmacology*
Neoplasms / metabolism*,  pathology*
Oxidation-Reduction / drug effects
Phenanthrolines / pharmacology
Skin Neoplasms / pathology
Chemical
Reg. No./Substance:
0/Free Radical Scavengers; 0/Naphthoquinones; 0/Phenanthrolines; 481-42-5/plumbagin; 484-11-7/neocuproine; 7440-50-8/Copper

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