IndraLab
Statements
Calcitriol inhibits KCNH1. 9 / 9
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"Therefore, the rationale of the combined therapy proposed herein is based on Eag1 gene expression inhibition by calcitriol, together with the functional blockade of K + currents through this particular channel by astemizole, in order to potentiate the antineoplastic effects of both compounds."
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"Thus, cell proliferation inhibition is one of the most important anti-cancer effects of the vitamin D endocrine system in cervical cancer.Previously, we have demonstrated that the oncogenic potassium channel ether a go-go-1 (EAG1) is down-regulated by calcitriol both in HeLa and SiHa cervical cancer cell lines [52], by a mechanism involving the repressive function of a negative VDRE in the EAG1 promoter [53]."
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"On the other hand, even if calcitriol consistently down-regulated Eag-1 in all cell lines tested, and the effect of both drugs combined upon inhibition of cell proliferation and Ki-67 expression was synergistic, the significant downregulation of Eag1 mRNA observed with the combination of astemizole plus calcitriol in IDC-1 was not detected in SUM-229PE cells."
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"Therefore, the rationale of the combined therapy proposed herein is based on Eag1 gene expression inhibition by calcitriol, together with the functional blockade of K + currents through this particular channel by astemizole, in order to potentiate the antineoplastic effects of both compounds."
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"In addition, calcitriol significantly inhibited tumoral EAG1 mRNA and protein expression, an effect that was further increased by the co-administration with astemizole, showing for the first time the in vivo inhibition of this oncogenic potassium channel by these drugs in breast tumors."