Dimeric naphthoquinones, a novel class of compounds with prostate cancer cytotoxicity.
BJU Int
; 108(3): 447-54, 2011 Aug.
Article
em En
| MEDLINE
| ID: mdl-21176082
ABSTRACT
OBJECTIVES:
⢠To evaluate the cytotoxicity of dimeric naphthoquinones (BiQs) in prostate cancer cells. ⢠To assess the interaction of dimeric naphthoquinones with common therapies including radiation and docetaxel. MATERIALS ANDMETHODS:
⢠The cytotoxicity of 12 different dimeric naphthoquinones was assessed in androgen-independent (PC-3, DU-145) and androgen-responsive (LNCaP, 22RV1) prostate cancer cell lines and in prostate epithelial cells (PrECs). ⢠BiQ2 and BiQ11 were selected for determination of dose response, effects on colony formation and initial exploration into mechanism of action. ⢠Synergistic effects with radiation and docetaxel were explored using colony-forming and MTT assays.RESULTS:
⢠At concentrations of 15µM, BiQ2, BiQ3, BiQ11, BiQ12, and BiQ15 demonstrated cytotoxicity in all prostate cancer cell lines. ⢠Treatment with BiQs limited the ability of prostate cancer cells to form colonies in clonogenic assays. ⢠Exposure of prostate cancer to BiQs increased cellular reactive oxygen species (ROS), decreased ATP production, and promoted apoptosis. ⢠BiQ cytotoxicity was independent of NADP(H)quinone oxidoreductase 1 (NQO1) activity in PrECs, PC-3 and 22RV1, but not DU-145 cells. ⢠Exposure of prostate cancer cells to radiation before treatment with BiQs increased their activity allowing for inhibitory effects well below the IC(50) s of these compounds in PrECs. ⢠Co-administration of BiQs with docetaxel had minimal additive effects.CONCLUSIONS:
⢠Dimeric naphthoquinones represent a new class of compounds with prostate cancer cytotoxicity and synergistic effects with radiation. The cytotoxic effect of these agents is probably contributed to by the accumulation of ROS and mitochondrial dysfunction. ⢠Further studies are warranted to better characterize this class of potential chemo-therapeutics.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Neoplasias da Próstata
/
Naftoquinonas
/
Antineoplásicos
Limite:
Humans
/
Male
Idioma:
En
Revista:
BJU Int
Assunto da revista:
UROLOGIA
Ano de publicação:
2011
Tipo de documento:
Article
País de afiliação:
Estados Unidos