Calcitriol (Synonyms: 1,25-dihydroxy Cholecalciferol, 1α,25-dihydroxy Cholecalciferol, 1,25-dihydroxy Vitamin D3, 1α,25-dihydroxy Vitamin D3)

Calcitriol, as the most biologically active metabolite derived from the secosteroid hormone vitamin D, the inhibition of calcitriol caused decreased effects of anticancer drugs.^[1]

In vitro efficacy test it shown that weekly oral administration of calcitriol allowed reach the peak serum calcitriol concentrations well above 1 nM, a concentration that inhibition more than 50% of prostate cancer proliferation. ^[2] With 10 nM calcitriol remarkably decreased RAGE protein expression and increased sRAGE concentrations in HL-1 cardiomyocytes compared with control cells.^[3] Calcitriol exhibited antiproliferative effects against T47D, MCF-7, and MDA-MB-231 with IC50 values in the range of 0.05-0.25 μM.[4] In addition, calcitriol inhibits melanoma cell proliferation with an IC₅₀ of 0.24 μM.^[5] BT-474 cells were dose-dependently growth-inhibited by calcitriol with IC50 of 2.9 nM. With 1 nM Calcitriol synergistically improved AZD4547 antiproliferative effects, allowing a 2-fold AZD4547 dose-reduction. ^[6]

In vivo test it demonstrated that calcitriol (0.03 μg/kg) 5 times/wk intraperitoneally for 10 wk in UNX ApoE-/- mice caused significant vascular calcification and elevated expression of related proteins (BMP2, RANKL, and Runx2).^[8] With 0.5 ug/day calcitriol orally improved insulin resistance and HOMA-β after 6 months in ND patients, however, only improved HOMA-β in the dialysis patients, with no obvious effect on insulin resistance.^[7]

References:
[1]Ma J, et al. The mechanism of calcitriol in cancer prevention and treatment. Curr Med Chem. 2013;20(33):4121-30. 
[2]Beer TM. Development of weekly high-dose calcitriol based therapy for prostate cancer. Urol Oncol. 2003 Sep-Oct;21(5):399-405. 
[3]Lee TW, et al. ADAM10 modulates calcitriol-regulated RAGE in cardiomyocytes. Eur J Clin Invest. 2017 Sep;47(9):675-683.
[4]Aljunidee KA, et al. Combination therapy of calcitriol inhibits the proliferation of breast cancer cells: new concept of nonclassical function of calcitriol. Horm Mol Biol Clin Investig. 2021 Nov 15. 
[5]Sutedja EK, et al. Calcitriol Inhibits Proliferation and Potentially Induces Apoptosis in B16-F10 Cells. Med Sci Monit Basic Res. 2022 May 5;28:e935139.
  [6]Morales-Guadarrama G, et al. AZD4547 and calcitriol synergistically inhibited BT-474 cell proliferation while modified stemness and tumorsphere formation. J Steroid Biochem Mol Biol. 2022 May 31;223:106132.
[7]Lu Y, et al. Effects of active vitamin D on insulin resistance and islet β-cell function in non-diabetic chronic kidney disease patients: a randomized controlled study. Int Urol Nephrol. 2022 Jul;54(7):1725-1732.
[8]Becker LE, et al. Effect of paricalcitol and calcitriol on aortic wall remodeling in uninephrectomized ApoE knockout mice. Am J Physiol Renal Physiol. 2011 Mar;300(3):F772-82.