title: 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: Centre for Soybean Research of Partner State Key Laboratory of Agrobiotechnology and School of Life Sciences, The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong SAR, China.
authors: Qinglei
authors: Q
authors: Zhan
authors: Sauna
authors: S
authors: Tsai
authors: Yonghai
authors: Y
authors: Lu
authors: Chunmei
authors: C
authors: Wang
authors: Yiuwa
authors: Y
authors: Kwan
authors: Saiming
authors: S
authors: Ngai
mesh_terms: D000074183:ATPases Associated with Diverse Cellular Activities; D000107:Acetylation / Q000187:drug effects; D017209:Apoptosis / Q000187:drug effects*; D001572:Benzofurans / Q000494:pharmacology*; D015153:Blotting, Western; D002352:Carrier Proteins / Q000378:metabolism*; D045744:Cell Line, Tumor; D004265:DNA Helicases / Q000378:metabolism*; D059565:G2 Phase Cell Cycle Checkpoints / Q000187:drug effects; D056572:Histone Deacetylase Inhibitors / Q000494:pharmacology*; D006657:Histones / Q000378:metabolism; D006801:Humans; D006877:Hydroxamic Acids / Q000494:pharmacology*; D008297:Male; D008938:Mitosis / Q000187:drug effects; D008954:Models, Biological; D009363:Neoplasm Proteins / Q000378:metabolism; D009447:Neuroblastoma / Q000201:enzymology* / Q000378:metabolism / Q000473:pathology*; D040901:Proteomics; D015203:Reproducibility of Results; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D001572:Benzofurans; D002352:Carrier Proteins; D056572:Histone Deacetylase Inhibitors; D006657:Histones; D006877:Hydroxamic Acids; D009363:Neoplasm Proteins; D000074183:ATPases Associated with Diverse Cellular Activities; D004265:DNA Helicases; C122079:RUVBL2 protein, human; C512352:abexinostat
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