Vitamin D3

Vitamin D3 (Cholecalciferol; Colecalciferol) is a naturally occuring form of vitamin D. Vitamin D3 induces cell differentiation and prevents proliferation of cancer cells. In Vitro:Vitamin D3 is an inactive vitamin D molecule in vivo. Vitamin D3 undergoes two hydroxylation processes to activate it. Vitamin D3 is first hydroxylated in the liver to form the circulating prohormone 25-hydroxy vitamin D3 [25(OH)D3] by the enzyme 25-hydroxylase (CYP27A1) and probably also by other enzymes (e.g., CYP2R1)^[1].
The second hydroxylation occurs in the kidneys via the enzyme 1-alpha-hydroxylase, yielding 1,25- dihydroxycholecalciferol (calcitriol), which is the biologically active form of vitamin D^[1].
Vitamin D3 (2-10 μM; 24-48 hours) exhibits anti-proliferative effects in a dose- and time-dependent manner. Maximal reduction of viability post-treatment of 62% (IK), 52% (RL-95-2), and 55% (Hec-1A) occurs by 72 h of treatment with 10 μM Vitamin D3. but 24-hour exposure lacks significant reduction in viable cells^[2].
Cholecalciferol (10 μM; 24-48 hours) shows marked increases in nuclear VDR staining and produces local VDR activation in IK cells^[1].
In Vivo:Cholecalciferol (oral gavage; 5 mg/kg; 7 days) potentiates the CCl4 toxicity only in the liver, as indicated by plasma levels of ALT and AST, biochemical markers of hepatic damage. It significantly increases renal calcium levels in mice, but renal calcium content does not differ significantly between mice^[3].