Antiproliferative effect of 1,25-dihydroxyvitamin D3 and its analogs on human colon adenocarcinoma cells (CaCo-2): influence of extracellular calcium

Biochem Biophys Res Commun. 1991 Aug 30;179(1):57-62. doi: 10.1016/0006-291x(91)91333-8.


Depending on culture in either "low Ca++" (0.25 mM) or "normal Ca++" (1.8 mM) medium, human colon adenocarcinoma-derived CaCo-2 cells exhibit differential sensitivity to the antiproliferative action of 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) and of two side-chain modified analogs, 1,25S,26-trihydroxy-delta 22-vitamin D3 (Ro 23-4319) and 1,25-dihydroxy-delta 16-23yne-vitamin D3 (Ro 23-7553). CaCo-2 cells cultured under low Ca++ conditions exhibit a high proliferative potential, and in these cells, all vitamin D compounds under investigation significantly inhibit [3H]thymidine incorporation into cellular DNA at greater than or equal to 10(-10) M. The rank order of biopotency is: Ro 23-7553 greater than or equal to Ro 23-4319 greater than 1,25(OH)2D3. At 1.8 mM Ca++, only Ro 23-7553 is able to inhibit proliferation of CaCo-2 cells. Parallel to their antiproliferative action, all three vitamin D compounds stimulate akaline phosphatase activity in CaCo-2 cells, indicating their ability to induce differentiated functions at the same time as they reduce neoplastic cell growth.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma
  • Alkaline Phosphatase / metabolism
  • Calcitriol / analogs & derivatives*
  • Calcitriol / pharmacology*
  • Calcium / pharmacology*
  • Cell Division / drug effects
  • Cell Line
  • Colonic Neoplasms
  • Hydroxycholecalciferols / pharmacology*
  • Structure-Activity Relationship


  • Hydroxycholecalciferols
  • 1,24,26-trihydroxy-delta 22-vitamin D3
  • Alkaline Phosphatase
  • Calcitriol
  • Ro 23-7553
  • Calcium