| Valproic acid overcomes hypoxia-induced resistance to apoptosis. | |
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MedLine Citation:
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PMID: 22159638 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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Valproic acid (VPA), a histone deacetylase inhibitor (HDACi), has been shown to be an effective tool in cancer treatment. Although its ability to induce apoptosis has been described in many cancer types, the data come from experiments performed in normoxic (21% O2) conditions only. Therefore, we questioned whether VPA would be equally effective under hypoxic conditions (1% O2), which is known to induce resistance to apoptosis. Four neuroblastoma cell lines were used: UKF-NB-3, SK-N-AS, plus one cisplatin-resistant subline derived from each of the two original sensitive lines. All were treated with VPA and incubated under hypoxic conditions. Measurement of apoptosis and viability using TUNEL assay and Annexin V/propidium iodide labeling revealed that VPA was even more effective under hypoxic conditions. We show here that hypoxia-induced resistance to chemotherapeutic agents such as cisplatin could be overcome using VPA. We also demonstrated that apoptosis pathways induced by VPA do not differ between normoxic and hypoxic conditions. VPA-induced apoptosis proceeds through the mitochondrial pathway, not the extrinsic pathway (under both normoxia and hypoxia), since inhibition of caspase-8 failed to decrease apoptosis or influence bid cleavage. Our data demonstrated that VPA is more efficient in triggering apoptosis under hypoxic conditions and overcomes hypoxia-induced resistance to cisplatin. The results provide additional evidence for the use of VPA in neuroblastoma (NBL) treatment. |
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Authors:
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Simon Cipro; Jana Hřebačková; Jan Hraběta; Jitka Poljaková; Tomáš Eckschlager |
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Publication Detail:
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Type: JOURNAL ARTICLE Date: 2011-12-06 |
Journal Detail:
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Title: Oncology reports Volume: - ISSN: 1791-2431 ISO Abbreviation: - Publication Date: 2011 Dec |
Date Detail:
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Created Date: 2011-12-13 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 9422756 Medline TA: Oncol Rep Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Affiliation:
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Department of Pediatric Hematology and Oncology, 2nd Medical School, Charles University and University Hospital Motol, V Úvalu 84, 150 00 Prague 5, Czech Republic. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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