Abstract
Abstract Introduction: Ether à go-go 1 (Eag1) channels have oncogenic properties. This channel is widely expressed in human tumors. It has been shown that inhibition of its expression and/or activity reduces cellular proliferation. Some cancer-associated factors up-regulate Eag1 expression; including estradiol and the E6 and E7 human papilloma virus (HPV) oncogenes. On the other hand, calcitriol (the most active metabolite of vitamin D) has shown antiproliferative properties and it has been considered as a potential anticancer treatment. In this work, we studied Eag1 regulation by estradiol, tamoxifen, ICI 182 780, genistein and calcitriol in the cervical cancer cell line SiHa, that express E6 an E7 HPV oncogenes. Methods: SiHa cells were cultivated with DMEM without phenol red and were treated with estradiol, tamoxifen, ICI 182 780, genistein or calcitriol during 48 hours. Total RNA was obtained with Trizol reagent, and cDNA was synthesized. Eag1 expression was evaluated by real time PCR. Eag1 expression was normalized against the housekeeping gene GAPDH. Using XTT colorimetric assay we evaluated the effect of calcitriol on SiHa cells proliferation. Results: Calcitriol decreased cell proliferation after 5 days of culture. We also identified estrogen receptors α and β and VDR (vitamin D receptor) proteins by Western blot. Estradiol, antiestrogens, genistein and calcitriol down-regulated Eag1 mRNA expression. Concomitant treatment of SiHa cells with estradiol and calcitriol seems to potentiate such Eag1 down-regulation. On the other hand, SiHa cells expressed higher levels of ERβ than ERα. Conclusions: Our data suggest that down regulation of Eag1 by calcitriol could be a new mechanism by which calcitriol reduce tumor cells proliferation. Together, estradiol, antiestrogens, genistein and calcitriol could be used as treatment for cancers that present ER pattern expression silimar to SiHa cells. Citation Information: Cancer Res 2009;69(23 Suppl):A67.
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