| Plumbagin and juglone induce caspase-3-dependent apoptosis involving the mitochondria through ROS generation in human peripheral blood lymphocytes. | |
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MedLine Citation:
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PMID: 21982843 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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The phytochemicals plumbagin and juglone have recently been gaining importance because of their various pharmacological activities. In this study, these compounds are shown to induce concentration- and time-dependent toxicity in human peripheral blood lymphocytes via the apoptotic pathway. Flow cytometry data revealed the occurrence of about 28% early apoptotic cells after 6h exposure to 10μM plumbagin and 35% late apoptotic cells and about 43% sub-G1 population after 24h. The cytotoxic effect of plumbagin was at least twofold higher than that of juglone as evidenced by the IC(50) value for cytotoxicity. Characteristic apoptotic features such as chromatin condensation and apoptotic body formation were observed through TEM, and membrane blebbing and cell surface smoothening were seen in SEM studies. Generation of ROS was evidenced through the HPLC analysis of superoxide-specific 2-OH-E+ formation. In addition, a decrease in GSH levels parallel to ROS production was observed. Reversal of apoptosis in both NAC- and Tempol-pretreated cells indicates the involvement of both ROS generation and GSH depletion in plumbagin- and juglone-induced apoptosis. The mechanistic pathway involves a decrease in MMP; alterations in the levels of Bcl-2, Bax, and cytosolic cytochrome c; and PARP-1 cleavage subsequent to caspase-3 activation. |
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Authors:
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Priya Seshadri; Anantanarayanan Rajaram; Rama Rajaram |
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Publication Detail:
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Type: JOURNAL ARTICLE Date: 2011-9-16 |
Journal Detail:
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Title: Free radical biology & medicine Volume: - ISSN: 1873-4596 ISO Abbreviation: - Publication Date: 2011 Sep |
Date Detail:
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Created Date: 2011-10-10 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 8709159 Medline TA: Free Radic Biol Med Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Copyright Information:
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Copyright © 2011 Elsevier Inc. All rights reserved. |
Affiliation:
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Biochemistry Laboratory, Central Leather Research Institute, Adyar, Chennai 600 020, India. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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