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).
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.
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) occurrs by 72 h of treatment with 10 μM Vitamin D3. but 24-hour exposure lacks significant reduction in viable cells.
Cholecalciferol (10 μM; 24-48 hours) shows marked increases in nuclear VDR staining and produces local VDR activation in IK cells.
Cell Viability Assay
Cell Line: |
EC cell lines from EEC, Ishikawa 3-H-12(IK), RL-95/2, and HEC-1-A cells |
Concentration: |
2-10 μM |
Incubation Time: |
24-72 hours |
Result: |
Reduced viability in response to VD3 in a dose- and time-dependent manner. Indicated that the conversion of VD3 to 25(OH)D is an essential step for the reduced cell viability effect. |
Cell Viability Assay
Cell Line: |
EC cell lines from EEC, Ishikawa 3-H-12(IK) cells |
Concentration: |
10 μM |
Incubation Time: |
24-48 hours |
Result: |
Improved nuclear VDR content in IK cells. |