Antiproliferative effect of 1,25-dihydroxyvitamin D3 and its analogs on human colon adenocarcinoma cells (CaCo-2): influence of extracellular calcium.
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.
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Department of General and Experimental Pathology, University of Vienna Medical School, Austria.
Huber
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Peterlik
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D000230:Adenocarcinoma; D000469:Alkaline Phosphatase / Q000378:metabolism; D002117:Calcitriol / Q000031:analogs & derivatives* / Q000494:pharmacology*; D002118:Calcium / Q000494:pharmacology*; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D003110:Colonic Neoplasms; D006887:Hydroxycholecalciferols / Q000494:pharmacology*; D013329:Structure-Activity Relationship
D006887:Hydroxycholecalciferols; C070643:1,24,26-trihydroxy-delta 22-vitamin D3; D000469:Alkaline Phosphatase; D002117:Calcitriol; C064183:Ro 23-7553; D002118:Calcium