PMID- 25277659
OWN - NLM
STAT- MEDLINE
DCOM- 20150612
LR  - 20211021
IS  - 1423-0380 (Electronic)
IS  - 1010-4283 (Linking)
VI  - 36
IP  - 2
DP  - 2015 Feb
TI  - AZD1152-HQPA induces growth arrest and apoptosis in androgen-dependent prostate 
      cancer cell line (LNCaP) via producing aneugenic micronuclei and polyploidy.
PG  - 623-32
LID - 10.1007/s13277-014-2664-8 [doi]
AB  - Prostate cancer is the frequent non-cutaneous tumor with high mortality in men. 
      Prostate tumors contain cells with different status of androgen receptor. 
      Androgen receptor plays important roles in progression and treatment of prostate 
      cancer. Aurora B kinase, with oncogenic potential, is involved in chromosome 
      segregation and cytokinesis, and its inhibition is a promising anti-cancer 
      therapy. In the present study, we aimed to investigate the effects of Aurora B 
      inhibitor, AZD1152-HQPA, on survival and proliferation of androgen receptor 
      (AR)-positive prostate cancer cells. LNCaP was used as androgen-dependent 
      prostate cancer cell line. We explored the effects of AZD1152-HQPA on cell 
      viability, DNA content, micronuclei formation, and expression of genes involved 
      in apoptosis and cell cycle. Moreover, the expression of Aurora B and AR were 
      investigated in 23 benign prostatic hyperplasia and 38 prostate cancer specimens. 
      AZD1152-HQPA treatment induced defective cell survival, polyploidy, and cell 
      death in LNCaP cell line. Centromeric labeling with fluorescence in situ 
      hybridization (FISH) showed that the loss of whole chromosomes is the origin of 
      micronuclei, indicating on aneugenic action of AZD1152-HQPA. Treatment of 
      AZD1152-HQPA decreased expression of AR. Moreover, we found weak positive 
      correlations between the expression of Aurora B and AR in both benign prostatic 
      hyperplasia and prostate cancer specimens (r = 0.25, r = 0.41). This is the first 
      time to show that AZD1152-HQPA can be a useful therapeutic strategy for the 
      treatment of androgen-dependent prostate cancer cell line. AZD1152-HQPA induces 
      aneugenic mechanism of micronuclei production. Taken together, this study 
      provides new insight into the direction to overcome the therapeutic impediments 
      against prostate cancer.
FAU - Zekri, Ali
AU  - Zekri A
AD  - Department of Medical Genetics, Tehran University of Medical Sciences, Tehran, 
      Iran.
FAU - Ghaffari, Seyed H
AU  - Ghaffari SH
FAU - Ghanizadeh-Vesali, Samad
AU  - Ghanizadeh-Vesali S
FAU - Yaghmaie, Marjan
AU  - Yaghmaie M
FAU - Salmaninejad, Arash
AU  - Salmaninejad A
FAU - Alimoghaddam, Kamran
AU  - Alimoghaddam K
FAU - Modarressi, Mohammad H
AU  - Modarressi MH
FAU - Ghavamzadeh, Ardeshir
AU  - Ghavamzadeh A
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20141003
PL  - Netherlands
TA  - Tumour Biol
JT  - Tumour biology : the journal of the International Society for Oncodevelopmental 
      Biology and Medicine
JID - 8409922
RN  - 0 
      (2-((3-((4-((5-(2-((3-fluorophenyl)amino)-2-oxoethyl)-1H-pyrazol-3-yl)amino)quinazolin-7-yl)oxy)propyl)(ethyl)amino)ethyl 
      dihydrogen phosphate)
RN  - 0 (Aneugens)
RN  - 0 (Organophosphates)
RN  - 0 (Quinazolines)
RN  - 0 (Receptors, Androgen)
RN  - EC 2.7.11.1 (AURKB protein, human)
RN  - EC 2.7.11.1 (Aurora Kinase B)
SB  - IM
MH  - Aneugens/administration & dosage
MH  - Animals
MH  - Apoptosis/drug effects
MH  - Aurora Kinase B/*biosynthesis/genetics
MH  - Cell Line, Tumor
MH  - Cell Survival/drug effects
MH  - Gene Expression Regulation, Neoplastic/drug effects
MH  - Humans
MH  - In Situ Hybridization, Fluorescence
MH  - Male
MH  - Mice
MH  - Micronuclei, Chromosome-Defective/drug effects
MH  - Organophosphates/*administration & dosage
MH  - Prostatic Neoplasms/*drug therapy/genetics/pathology
MH  - Quinazolines/*administration & dosage
MH  - Receptors, Androgen/*biosynthesis/genetics
MH  - Xenograft Model Antitumor Assays
EDAT- 2014/10/04 06:00
MHDA- 2015/06/13 06:00
CRDT- 2014/10/04 06:00
PHST- 2014/07/11 00:00 [received]
PHST- 2014/09/19 00:00 [accepted]
PHST- 2014/10/04 06:00 [entrez]
PHST- 2014/10/04 06:00 [pubmed]
PHST- 2015/06/13 06:00 [medline]
AID - 10.1007/s13277-014-2664-8 [doi]
PST - ppublish
SO  - Tumour Biol. 2015 Feb;36(2):623-32. doi: 10.1007/s13277-014-2664-8. Epub 2014 Oct 
      3.