ABSTRACT
Cancer is a leading cause of death worldwide. New early tumor markers are needed to treat the disease at curable stages. In addition, new therapeutic targets are required to treat patients not responding to available treatments. Ion channels play major roles in health and disease, including cancer. Actually, several ion channels have been suggested as potential tumor markers and therapeutic targets for different types of malignancies. One of most studied ion channels in cancer is the voltage-gated potassium channel Eag1 (ether à go-go 1), which has a high potential to be used as a cancer biomarker. Eag1 is expressed in most human tumors, in contrast to its restricted distribution in healthy tissues. Several findings suggest Eag1 as a potential early marker for cervical, colon, and breast cancer. In addition, because Eag1 amplification/expression is associated with poor survival in leukemia, colon and ovarian cancer patients, it has also been proposed as a prognosis marker. Moreover, inhibition of either expression or activity of Eag1 leads to reduced proliferation of cancer cells, making Eag1 a potential anticancer target. Using Eag1 in cancer detection programs could help to reduce mortality from this disease.
Subject(s)
Biomarkers, Tumor/analysis , Ether-A-Go-Go Potassium Channels/analysis , Neoplasms/diagnosis , Biomarkers, Tumor/genetics , Ether-A-Go-Go Potassium Channels/genetics , Humans , PrognosisABSTRACT
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.
