Calcitriol down-regulates human ether a go-go 1 potassium channel expression in cervical cancer cells.
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.
Avila
Euclides
E
Department of Reproductive Biology, Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran, Tlalpan 14000 Mexico, D.F., Mexico.
García-Becerra
Rocío
R
Rodríguez-Rasgado
Jesús Adrián
JA
Díaz
Lorenza
L
Ordaz-Rosado
David
D
Zügel
Ulrich
U
Steinmeyer
Andreas
A
Barrera
David
D
Halhali
Ali
A
Larrea
Fernando
F
Camacho
Javier
J
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*
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