Journal
ONCOLOGY REPORTS
Volume 27, Issue 4, Pages 1219-1226Publisher
SPANDIDOS PUBL LTD
DOI: 10.3892/or.2011.1577
Keywords
valproic acid; hypoxia; apoptosis; neuroblastoma
Categories
Funding
- [GAUK 72208/2008]
- [GACR P301/10/0356]
Ask authors/readers for more resources
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% O-2) conditions only. Therefore, we questioned whether VPA would be equally effective under hypoxic conditions (1% O-2), 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.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available