Suppression of RelB-mediated manganese superoxide dismutase expression reveals a primary mechanism for radiosensitization effect of 1alpha,25-dihydroxyvitamin D(3) in prostate cancer cells.
Mol Cancer Ther
; 6(7): 2048-56, 2007 Jul.
Article
em En
| MEDLINE
| ID: mdl-17604335
ABSTRACT
Nuclear factor-kappaB provides an adaptive response to protect cancer cells against cytotoxicity induced by redox active therapeutics. RelB is uniquely expressed at a high level in prostate cancer with high Gleason scores. Recently, we showed that the level of RelB rapidly increases in androgen-independent prostate cancer cells after exposure to ionizing radiation (IR), leading to a reduction in intrinsic radiosensitivity. Here, we show that interaction of 1alpha,25-dihydroxyvitamin D(3) [1alpha,25-(OH)(2)D(3)] with the vitamin D receptor significantly enhances radiosensitivity of prostate cancer cells at clinically relevant radiation doses. The radiosensitization effect of 1alpha,25-(OH)(2)D(3) is mediated, at least in part, by selectively suppressing IR-mediated RelB activation, leading to a reduced expression of its target gene MnSOD, a primary antioxidant enzyme in mitochondria. These results suggest that suppression of manganese superoxide dismutase is a mechanism by which 1alpha,25-(OH)(2)D(3) exerts its radiosensitization effect and that 1alpha,25-(OH)(2)D(3) may serve as an effective pharmacologic agent for selectively sensitizing prostate cancer cells to IR via suppression of antioxidant responses in mitochondria.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Neoplasias da Próstata
/
Tolerância a Radiação
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Superóxido Dismutase
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Vitamina D
/
Fator de Transcrição RelB
Limite:
Humans
/
Male
Idioma:
En
Revista:
Mol Cancer Ther
Assunto da revista:
ANTINEOPLASICOS
Ano de publicação:
2007
Tipo de documento:
Article
País de afiliação:
Estados Unidos