Interaction of retinoic acid and vitamin D3 analogs on HL-60 myeloid leukemic cells.
Retinoic acid (RA) is an interesting agent which has been shown to induce differentiation and complete remission in patients with acute promyelocytic leukemia. 1,25-(OH)2-delta 16-23-yne-cholecalciferol (16-23-D3) and 1,25-(OH)2-23-yne-cholecalciferol (23-D3) are vitamin D3 analogs capable of inducing differentiation of myeloid leukemic cells with little effect on either calcium absorption or mobilization. Using HL-60 myeloid leukemic cells as in vitro model for human acute myeloid leukemia we observed an additive to synergistic interaction between RA and 16-23-D3 or 23-D3 with respect to the inhibition of cell growth and DNA synthesis, the induction of differentiation and the loss of cell clonogenicity. In addition, we observed that RA and 16-23-D3 interact additively with respect to the reduction of c-myc mRNA expression. These results suggest that Ra used in combination with 16-23-D3 or 23-D3 may be an interesting chemotherapeutic regimen to evaluate in patients with acute myeloid leukemia.
Département de pharmacologie, Université de Montréal, Québec, Canada.
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D002455:Cell Division / Q000187:drug effects; D002762:Cholecalciferol / Q000494:pharmacology*; D016259:Genes, myc; D006801:Humans; D015473:Leukemia, Promyelocytic, Acute / Q000235:genetics / Q000473:pathology*; D012333:RNA, Messenger / Q000032:analysis; D012334:RNA, Neoplasm / Q000032:analysis; D014212:Tretinoin / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
D012333:RNA, Messenger; D012334:RNA, Neoplasm; D002762:Cholecalciferol; D014212:Tretinoin