| Parthenolide induces caspase-independent and AIF-mediated cell death in human osteosarcoma and melanoma cells. | |
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MedLine Citation:
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PMID: 22688575 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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The mechanism of the cytotoxic effect exerted by parthenolide on tumor cells is not clearly defined today. This paper shows that parthenolide stimulates in human osteosarcoma MG63 and melanoma SK-MEL-28 cells a mechanism of cell death, which is not prevented by z-VAD-fmk and other caspase inhibitors. In particular treatment with parthenolide rapidly stimulated (1-2 h) ROS generation by inducing activation of extracellular signal-regulated kinase1/2 (ERK1/2) and NADPH oxidase. This event caused depletion of thiol groups and glutathione, NF-κB inhibition, JNK activation, cell detachment from the matrix and cellular shrinkage. The increase of ROS generation together with the mitochondrial accumulation of Ca(2+) also favoured dissipation of ▵ψm, which seemed primarily determined by PTP opening, since ▵ψm loss was partially prevented by the inhibitor cyclosporin A. Staining with Hoechst 33342 revealed in most cells, at 3-5h of treatment, chromatin condensation and fragmentation, while only few cells were PI-positive. In addition, at this stage AIF translocated to the nucleus and co-localized with areas of condensed chromatin. Prolonging the treatment (5-15h) ATP content declined while PI-positive cells strongly augmented, denouncing the increase of necrotic effects. All these effects were prevented by NAC, while caspase inhibitors were ineffective. We suggest that AIF exerts a crucial role in parthenolide action. In accordance, down-regulation of AIF markedly inhibited parthenolide effect on the production of cells with apoptotic or necrotic signs. Taken together our results demonstrate that parthenolide causes in the two cell lines a caspase-independent cell death, which is mediated by AIF. J. Cell. Physiol. © 2012 Wiley Periodicals, Inc. |
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Authors:
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Antonella D'Anneo; Daniela Carlisi; Marianna Lauricella; Sonia Emanuele; Riccardo Di Fiore; Renza Vento; Giovanni Tesoriere |
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Publication Detail:
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Type: JOURNAL ARTICLE Date: 2012-6-11 |
Journal Detail:
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Title: Journal of cellular physiology Volume: - ISSN: 1097-4652 ISO Abbreviation: - Publication Date: 2012 Jun |
Date Detail:
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Created Date: 2012-6-12 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 0050222 Medline TA: J Cell Physiol Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Copyright Information:
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Copyright © 2012 Wiley Periodicals, Inc. |
Affiliation:
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Dipartimento di Biomedicina Sperimentale e Neuroscienze Cliniche, Sezione di Scienze Biochimiche. Università degli Studi di Palermo, Italy. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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