RESUMO

BACKGROUND/AIM: Human ether à-go-go-1 (EAG1) potassium channels are promising anticancer targets. Calcitriol has antitumoural properties. This study investigated EAG1 regulation by calcitriol in normal and cancer cells. MATERIALS AND METHODS: Cancer cell lines from cervix, prostate, mammary gland, and normal placenta trophoblasts were cultured. Calcitriol was determined by HPLC. Gene and protein expression were assessed by real-time RT-PCR and western blot analysis, respectively. Calcitriol-synthesising enzyme CYP27B1 or vitamin D receptor (VDR), were transfected in cervical cancer SiHa cells. Cell proliferation was assayed with XTT. RESULTS: Calcitriol decreased EAG1 mRNA in all cell types, and EAG1 protein and proliferation in SiHa cells. VDR antagonist ZK-159222 prevented the calcitriol effect on EAG1 mRNA. CYP27B1-transfected cells produced more calcitriol and less EAG1 mRNA. EAG1 mRNA was more potently inhibited by calcitriol in VDR-transfected cells. CONCLUSION: EAG1 is a calcitriol target in normal and cancer cells and calcitriol is a potential therapy for cervical cancer.

Assuntos

Calcitriol/farmacologia , Canais de Potássio Éter-A-Go-Go/biossíntese , Neoplasias do Colo do Útero/metabolismo , 25-Hidroxivitamina D3 1-alfa-Hidroxilase/biossíntese , 25-Hidroxivitamina D3 1-alfa-Hidroxilase/genética , 25-Hidroxivitamina D3 1-alfa-Hidroxilase/metabolismo , Neoplasias da Mama/genética , Neoplasias da Mama/metabolismo , Calcitriol/análogos & derivados , Calcitriol/metabolismo , Linhagem Celular Tumoral , Regulação para Baixo/efeitos dos fármacos , Canais de Potássio Éter-A-Go-Go/genética , Feminino , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Células HeLa , Humanos , Masculino , Neoplasias da Próstata/genética , Neoplasias da Próstata/metabolismo , RNA Mensageiro/biossíntese , RNA Mensageiro/genética , Receptores de Calcitriol/antagonistas & inibidores , Receptores de Calcitriol/biossíntese , Receptores de Calcitriol/genética , Receptores de Calcitriol/metabolismo , Transfecção , Neoplasias do Colo do Útero/tratamento farmacológico , Neoplasias do Colo do Útero/genética