Enhancement of radiosensitivity by a unique novel NF-B inhibitor, DHMEQ, in prostate cancer

N. Kozakai, Eiji Kikuchi, M. Hasegawa, E. Suzuki, H. Ide, A. Miyajima, Y. Horiguchi, J. Nakashima, K. Umezawa, Naoyuki Shigematsu, Mototsugu Oya

Research output: Contribution to journalArticle

26 Citations (Scopus)

Abstract

Background: Inducible activation of nuclear factor (NF)-B is one of the principal mechanisms through which resistant prostate cancer cells are protected from radiotherapy. We hypothesised that inactivation of inducible NF-B with a novel NF-B inhibitor, DHMEQ, would increase the therapeutic effects of radiotherapy.Methods:PC-3 and LNCaP cells were exposed to irradiation and/or DHMEQ. Cell viability, cell cycle analysis, western blotting assay, and NF-B activity were measured. The antitumour effect of irradiation combined with DHMEQ in vivo was also assessed.Results:The combination of DHMEQ with irradiation resulted in cell growth inhibition and G2/M arrest relative to treatment with irradiation alone. Inducible NF-B activity by irradiation was inhibited by DHMEQ treatment. The expression of p53 and p21 in LNCaP, and of 14-3-3 in PC-3 cells, was increased in the combination treatment. In the in vivo study, 64 days after the start of treatment, tumour size was 85.1%, 77.1%, and 64.7% smaller in the combination treatment group than that of the untreated control, DHMEQ-treated alone, and irradiation alone groups, respectively.Conclusion:Blockade of NF-B activity induced by radiation with DHMEQ could overcome radio-resistant responses and may become a new therapeutic modality for treating prostate cancer.

Original languageEnglish
Pages (from-to)652-657
Number of pages6
JournalBritish Journal of Cancer
Volume107
Issue number4
DOIs
Publication statusPublished - 2012 Aug 7

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Radiation Tolerance
Prostatic Neoplasms
Radiotherapy
Therapeutics
Therapeutic Uses
Radio
Cell Survival
Cell Cycle
Western Blotting
Radiation
Control Groups
Growth
Neoplasms

Keywords

  • nuclear factor-κB
  • prostate cancer
  • radiation

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Enhancement of radiosensitivity by a unique novel NF-B inhibitor, DHMEQ, in prostate cancer. / Kozakai, N.; Kikuchi, Eiji; Hasegawa, M.; Suzuki, E.; Ide, H.; Miyajima, A.; Horiguchi, Y.; Nakashima, J.; Umezawa, K.; Shigematsu, Naoyuki; Oya, Mototsugu.

In: British Journal of Cancer, Vol. 107, No. 4, 07.08.2012, p. 652-657.

Research output: Contribution to journalArticle

Kozakai, N, Kikuchi, E, Hasegawa, M, Suzuki, E, Ide, H, Miyajima, A, Horiguchi, Y, Nakashima, J, Umezawa, K, Shigematsu, N & Oya, M 2012, 'Enhancement of radiosensitivity by a unique novel NF-B inhibitor, DHMEQ, in prostate cancer', British Journal of Cancer, vol. 107, no. 4, pp. 652-657. https://doi.org/10.1038/bjc.2012.321
Kozakai, N. ; Kikuchi, Eiji ; Hasegawa, M. ; Suzuki, E. ; Ide, H. ; Miyajima, A. ; Horiguchi, Y. ; Nakashima, J. ; Umezawa, K. ; Shigematsu, Naoyuki ; Oya, Mototsugu. / Enhancement of radiosensitivity by a unique novel NF-B inhibitor, DHMEQ, in prostate cancer. In: British Journal of Cancer. 2012 ; Vol. 107, No. 4. pp. 652-657.
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