Calcitriol down-regulates human ether a go-go 1 potassium channel expression in cervical cancer cells

Anticancer Res. 2010 Jul;30(7):2667-72.

Abstract

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.

MeSH terms

  • 25-Hydroxyvitamin D3 1-alpha-Hydroxylase / biosynthesis
  • 25-Hydroxyvitamin D3 1-alpha-Hydroxylase / genetics
  • 25-Hydroxyvitamin D3 1-alpha-Hydroxylase / metabolism
  • Breast Neoplasms / genetics
  • Breast Neoplasms / metabolism
  • Calcitriol / analogs & derivatives
  • Calcitriol / metabolism
  • Calcitriol / pharmacology*
  • Cell Line, Tumor
  • Down-Regulation / drug effects
  • Ether-A-Go-Go Potassium Channels / biosynthesis*
  • Ether-A-Go-Go Potassium Channels / genetics
  • Female
  • Gene Expression Regulation, Neoplastic / drug effects
  • HeLa Cells
  • Humans
  • Male
  • Prostatic Neoplasms / genetics
  • Prostatic Neoplasms / metabolism
  • RNA, Messenger / biosynthesis
  • RNA, Messenger / genetics
  • Receptors, Calcitriol / antagonists & inhibitors
  • Receptors, Calcitriol / biosynthesis
  • Receptors, Calcitriol / genetics
  • Receptors, Calcitriol / metabolism
  • Transfection
  • Uterine Cervical Neoplasms / drug therapy
  • Uterine Cervical Neoplasms / genetics
  • Uterine Cervical Neoplasms / metabolism*

Substances

  • Ether-A-Go-Go Potassium Channels
  • KCNH1 protein, human
  • RNA, Messenger
  • Receptors, Calcitriol
  • ZK159222
  • 25-Hydroxyvitamin D3 1-alpha-Hydroxylase
  • Calcitriol