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Molecules 2014, 19(7), 10011-10032; doi:10.3390/molecules190710011
Article

Plumbagin Modulates Leukemia Cell Redox Status

1,†
,
1,†
,
1
,
1
,
2
 and
3,*
1 Laboratoire de Biologie Moléculaire et Cellulaire du Cancer (LBMCC), Hôpital Kirchberg, 9, Rue Edward Steichen, L-2540 Luxembourg, Grand-Duchy of Luxembourg 2 Laboratoire Structure et Réactivité des Systèmes Moléculaires Complexes, UMR CNRS 7565, Université de Lorraine, Campus Bridoux, Rue du Général Delestraint, F-57070 Metz, France 3 Department of Pharmacy, College of Pharmacy, Seoul National University, Seoul 151-742, Korea These authors contributed equally to this work.
* Author to whom correspondence should be addressed.
Received: 3 June 2014 / Revised: 20 June 2014 / Accepted: 25 June 2014 / Published: 10 July 2014
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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.
Keywords: plumbagin; natural products; leukemia; cancer; reactive oxygen species; glutathione; apoptosis; thiol groups plumbagin; natural products; leukemia; cancer; reactive oxygen species; glutathione; apoptosis; thiol groups
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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Gaascht, F.; Teiten, M.-H.; Cerella, C.; Dicato, M.; Bagrel, D.; Diederich, M. Plumbagin Modulates Leukemia Cell Redox Status. Molecules 2014, 19, 10011-10032.

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