title: Calcitriol down-regulates human ether a go-go 1 potassium channel expression in cervical cancer cells.
abstract: OBJECTIVE
  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.
  
  
  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.
  
  
  CONCLUSIONS
  EAG1 is a calcitriol target in normal and cancer cells and calcitriol is a potential therapy for cervical cancer.
authors.affiliation: Department of Reproductive Biology, Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran, Tlalpan 14000 Mexico, D.F., Mexico.
authors.forename: Euclides
authors.initials: E
authors.lastname: Avila
authors.forename: Rocío
authors.initials: R
authors.lastname: García-Becerra
authors.forename: Jesús Adrián
authors.initials: JA
authors.lastname: Rodríguez-Rasgado
authors.forename: Lorenza
authors.initials: L
authors.lastname: Díaz
authors.forename: David
authors.initials: D
authors.lastname: Ordaz-Rosado
authors.forename: Ulrich
authors.initials: U
authors.lastname: Zügel
authors.forename: Andreas
authors.initials: A
authors.lastname: Steinmeyer
authors.forename: David
authors.initials: D
authors.lastname: Barrera
authors.forename: Ali
authors.initials: A
authors.lastname: Halhali
authors.forename: Fernando
authors.initials: F
authors.lastname: Larrea
authors.forename: Javier
authors.initials: J
authors.lastname: Camacho
mesh_terms: D015090:25-Hydroxyvitamin D3 1-alpha-Hydroxylase / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism; D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism; D002117:Calcitriol / Q000031:analogs & derivatives / Q000378:metabolism / Q000494:pharmacology*; D045744:Cell Line, Tumor; D015536:Down-Regulation / Q000187:drug effects; D051638:Ether-A-Go-Go Potassium Channels / Q000096:biosynthesis* / Q000235:genetics; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006367:HeLa Cells; D006801:Humans; D008297:Male; D011471:Prostatic Neoplasms / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D018167:Receptors, Calcitriol / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism; D014162:Transfection; D002583:Uterine Cervical Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism*
chemical_list: D051638:Ether-A-Go-Go Potassium Channels; C496884:KCNH1 protein, human; D012333:RNA, Messenger; D018167:Receptors, Calcitriol; C410228:ZK159222; D015090:25-Hydroxyvitamin D3 1-alpha-Hydroxylase; D002117:Calcitriol