RuvBL2 is involved in histone deacetylase inhibitor PCI-24781-induced cell death in SK-N-DZ neuroblastoma cells.

Abstract

Neuroblastoma is the second most common solid tumor diagnosed during infancy. The survival rate among children with high-risk neuroblastoma is less than 40%, highlighting the urgent needs for new treatment strategies. PCI-24781 is a novel hydroxamic acid-based histone deacetylase (HDAC) inhibitor that has high efficacy and safety for cancer treatment. However, the underlying mechanisms of PCI-24781 are not clearly elucidated in neuroblastoma cells. In the present study, we demonstrated that PCI-24781 treatment significantly inhibited tumor growth at very low doses in neuroblastoma cells SK-N-DZ, not in normal cell line HS-68. However, PCI-24781 caused the accumulation of acetylated histone H3 both in SK-N-DZ and HS-68 cell line. Treatment of SK-N-DZ with PCI-24781 also induced cell cycle arrest in G2/M phase and activated apoptosis signaling pathways via the up-regulation of DR4, p21, p53 and caspase 3. Further proteomic analysis revealed differential protein expression profiles between non-treated and PCI-24781 treated SK-N-DZ cells. Totally 42 differentially expressed proteins were identified by MALDI-TOF MS system. Western blotting confirmed the expression level of five candidate proteins including prohibitin, hHR23a, RuvBL2, TRAP1 and PDCD6IP. Selective knockdown of RuvBL2 rescued cells from PCI-24781-induced cell death, implying that RuvBL2 might play an important role in anti-tumor activity of PCI-24781 in SK-N-DZ cells. The present results provide a new insight into the potential mechanism of PCI-24781 in SK-N-DZ cell line.

• Authors: Qinglei Zhan, Sauna Tsai, Yonghai Lu, Chunmei Wang, Yiuwa Kwan, Saiming Ngai
• Journal: PloS one (PLoS One) Vol. 8 Issue 8 Pg. e71663 ( 2013) ISSN: 1932-6203 [Electronic] United States
• PMID: 23977108 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Benzofurans
• Carrier Proteins
• Histone Deacetylase Inhibitors
• Histones
• Hydroxamic Acids
• Neoplasm Proteins
• ATPases Associated with Diverse Cellular Activities
• DNA Helicases
• RUVBL2 protein, human
• abexinostat

Topics

• ATPases Associated with Diverse Cellular Activities
• Acetylation (drug effects)
• Apoptosis (drug effects)
• Benzofurans (pharmacology)
• Blotting, Western
• Carrier Proteins (metabolism)
• Cell Line, Tumor
• DNA Helicases (metabolism)
• G2 Phase Cell Cycle Checkpoints (drug effects)
• Histone Deacetylase Inhibitors (pharmacology)
• Histones (metabolism)
• Humans
• Hydroxamic Acids (pharmacology)
• Male
• Mitosis (drug effects)
• Models, Biological
• Neoplasm Proteins (metabolism)
• Neuroblastoma (enzymology, metabolism, pathology)
• Proteomics
• Reproducibility of Results
• Signal Transduction (drug effects)