title: Plumbagin modulates leukemia cell redox status.
abstract: Plumbagin is a plant naphtoquinone exerting anti-cancer properties including apoptotic cell death induction and generation of reactive oxygen species (ROS). The aim of this study was to elucidate parameters explaining the differential leukemia cell sensitivity towards this compound. Among several leukemia cell lines, U937 monocytic leukemia cells appeared more sensitive to plumbagin treatment in terms of cytotoxicity and level of apoptotic cell death compared to more resistant Raji Burkitt lymphoma cells. Moreover, U937 cells exhibited a ten-fold higher ROS production compared to Raji. Neither differential incorporation, nor efflux of plumbagin was detected. Pre-treatment with thiol-containing antioxidants prevented ROS production and subsequent induction of cell death by apoptosis whereas non-thiol-containing antioxidants remained ineffective in both cellular models. We conclude that the anticancer potential of plumbagin is driven by pro-oxidant activities related to the cellular thiolstat.
authors.affiliation: Laboratoire de Biologie Moléculaire et Cellulaire du Cancer (LBMCC), Hôpital Kirchberg, 9, Rue Edward Steichen, L-2540 Luxembourg, Grand-Duchy of Luxembourg. francois.gaascht@lbmcc.lu.
authors.forename: François
authors.initials: F
authors.lastname: Gaascht
authors.affiliation: Laboratoire de Biologie Moléculaire et Cellulaire du Cancer (LBMCC), Hôpital Kirchberg, 9, Rue Edward Steichen, L-2540 Luxembourg, Grand-Duchy of Luxembourg. marie_helene.teiten@lbmcc.lu.
authors.forename: Marie-Hélène
authors.initials: MH
authors.lastname: Teiten
authors.affiliation: Laboratoire de Biologie Moléculaire et Cellulaire du Cancer (LBMCC), Hôpital Kirchberg, 9, Rue Edward Steichen, L-2540 Luxembourg, Grand-Duchy of Luxembourg. claudia.cerella@lbmcc.lu.
authors.forename: Claudia
authors.initials: C
authors.lastname: Cerella
authors.affiliation: Laboratoire de Biologie Moléculaire et Cellulaire du Cancer (LBMCC), Hôpital Kirchberg, 9, Rue Edward Steichen, L-2540 Luxembourg, Grand-Duchy of Luxembourg. mdicato@gmail.com.
authors.forename: Mario
authors.initials: M
authors.lastname: Dicato
authors.affiliation: Laboratoire Structure et Réactivité des Systèmes Moléculaires Complexes, UMR CNRS 7565, Université de Lorraine, Campus Bridoux, Rue du Général Delestraint, F-57070 Metz, France. denyse.bagrel@univ-lorraine.fr.
authors.forename: Denyse
authors.initials: D
authors.lastname: Bagrel
authors.affiliation: Department of Pharmacy, College of Pharmacy, Seoul National University, Seoul 151-742, Korea. marcdiederich@snu.ac.kr.
authors.forename: Marc
authors.initials: M
authors.lastname: Diederich
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D000975:Antioxidants / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D005978:Glutathione / Q000378:metabolism; D006801:Humans; D007938:Leukemia / Q000378:metabolism*; D009285:Naphthoquinones / Q000494:pharmacology*; D010084:Oxidation-Reduction / Q000187:drug effects*; D017382:Reactive Oxygen Species / Q000378:metabolism; D020298:U937 Cells
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D000975:Antioxidants; D009285:Naphthoquinones; D017382:Reactive Oxygen Species; D005978:Glutathione; C014758:plumbagin