Plumbagin-induced apoptosis in lymphocytes is mediated through increased reactive oxygen species production, upregulation of Fas, and activation of the caspase cascade
- Universite Catholique de Louvain and Cliniques Universitaires Saint-Luc, Brussels (Belgium)
- Division of Basic Medical Sciences, School of Medicine, Mercer University (United States)
- H. Lee Moffitt Cancer Center and Research Institute, MRC 2067, 12902 Magnolia Dr., Tampa, FL 33612 (United States)
Extracts from plants containing plumbagin (PLB) continue to be used as a treatment of a number of chronic immunologically-based diseases. However, most of these claims are supported only by anecdotal evidence with few scientific reports describing the mechanism of action or the efficacy of plumbagin in the suppression of the immune response. In the current study, we tested the hypothesis that plumbagin-induced suppression of the immune response was mediated through the induction of apoptosis. Splenocytes from C57BL/6 mice cultured in the presence of 0.5 {mu}M or greater concentrations of PLB significantly reduced proliferative responses to mitogens, including anti-CD3 mAbs, concanavalin A (Con A), lipopolysaccharide (LPS) and staphylococcal enterotoxin B (SEB) in vitro. Exposure of naive and activated splenocytes to PLB led to a significant increase in the levels of apoptosis. In addition, PLB treatment led to a significant increase in the levels of reactive oxygen species (ROS) in naive and activated splenocytes. Furthermore, treatment with the ROS scavenger, N-acetylcysteine (NAC), prevented PLB-induced apoptosis, suggesting a role of ROS in PLB-induced apoptosis. PLB-induced apoptosis led to ROS-mediated activation of both the extrinsic and intrinsic apoptotic pathways. In addition, plumbagin led to increased expression of Fas. Finally, treatment of mice with PLB (5 mg/kg) led to thymic and splenic atrophy as well as a significant suppression of the response to SEB and dinitroflourobenzene (DNFB) in vivo. Together, these results suggest that plumbagin has significant immunosuppressive properties which are mediated by generation of ROS, upregulation of Fas, and the induction of apoptosis.
- OSTI ID:
- 21460197
- Journal Information:
- Toxicology and Applied Pharmacology, Vol. 247, Issue 1; Other Information: DOI: 10.1016/j.taap.2010.05.013; PII: S0041-008X(10)00186-9; Copyright (c) 2010 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; ISSN 0041-008X
- Country of Publication:
- United States
- Language:
- English
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