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Tumor Biology

, Volume 36, Issue 2, pp 623–632 | Cite as

AZD1152-HQPA induces growth arrest and apoptosis in androgen-dependent prostate cancer cell line (LNCaP) via producing aneugenic micronuclei and polyploidy

  • Ali Zekri
  • Seyed H. Ghaffari
  • Samad Ghanizadeh-Vesali
  • Marjan Yaghmaie
  • Arash Salmaninejad
  • Kamran Alimoghaddam
  • Mohammad H. Modarressi
  • Ardeshir Ghavamzadeh
Research Article

Abstract

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.

Keywords

Aurora B kinase Prostate cancer Androgen receptor Apoptosis Weak positive correlations 

Notes

Acknowledgments

We sincerely thank AstraZeneca pharmaceutical company for providing AZD1152-HQPA. This study was supported by Hematology, Oncology and Stem Cell Transplantation Research Center, Tehran University of Medical Sciences, Tehran, Iran.

Conflicts of interest

None

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Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2014

Authors and Affiliations

  • Ali Zekri
    • 1
  • Seyed H. Ghaffari
    • 2
  • Samad Ghanizadeh-Vesali
    • 2
  • Marjan Yaghmaie
    • 2
  • Arash Salmaninejad
    • 1
  • Kamran Alimoghaddam
    • 2
  • Mohammad H. Modarressi
    • 1
  • Ardeshir Ghavamzadeh
    • 2
  1. 1.Department of Medical GeneticsTehran University of Medical SciencesTehranIran
  2. 2.Hematology, Oncology and Stem Cell Transplantation Research Center, Shariati HospitalTehran University of Medical SciencesTehranIran

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