title: Plumbagin induces cell death through a copper-redox cycle mechanism in human cancer cells.
abstract: 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.affiliation: Department of Biochemistry, Faculty of Life Sciences, Aligarh Muslim University, Aligarh 202002, Uttar Pradesh, India.
authors.forename: S
authors.initials: S
authors.lastname: Nazeem
authors.forename: Asfar S
authors.initials: AS
authors.lastname: Azmi
authors.forename: Sarmad
authors.initials: S
authors.lastname: Hanif
authors.forename: Aamir
authors.initials: A
authors.lastname: Ahmad
authors.forename: Ramzi M
authors.initials: RM
authors.lastname: Mohammad
authors.forename: S M
authors.initials: SM
authors.lastname: Hadi
authors.forename: K Sateesh
authors.initials: KS
authors.lastname: Kumar
mesh_terms: D016923:Cell Death / Q000187:drug effects; D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000187:drug effects / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects; D048430:Cell Shape / Q000187:drug effects; D020552:Comet Assay; D003300:Copper / Q000378:metabolism* / Q000494:pharmacology; D019610:Cytoprotection / Q000187:drug effects; D016166:Free Radical Scavengers / Q000494:pharmacology; D006801:Humans; D009285:Naphthoquinones / Q000494:pharmacology*; D009369:Neoplasms / Q000378:metabolism* / Q000473:pathology*; D010084:Oxidation-Reduction / Q000187:drug effects; D010618:Phenanthrolines / Q000494:pharmacology; D012878:Skin Neoplasms / Q000473:pathology
chemical_list: D016166:Free Radical Scavengers; D009285:Naphthoquinones; D010618:Phenanthrolines; D003300:Copper; C002701:neocuproine; C014758:plumbagin