DIFFERENTIATING EFFECTS OF 1,25-DIHYDROXYCHOLECALCIFEROL (D-3) ON LA-N-5 HUMAN NEUROBLASTOMA-CELLS AND ITS SYNERGY WITH RETINOIC ACID

Purpose: 1,25-Dihydroxycholecalciferol (D-3) plays an important role i n embryonic development and cell differentiation. It has previously be en reported to decrease c-myc expression by HL-60 cells and downregula te c-myc expression by breast and ovarian cancer cells. We report the results of our investigations into the differentiating effects of D-3 on LA-N-5 human neuroblastoma cells. Methods: LA-N-5 human neuroblasto ma cell line was treated with D-3, retinoic acid (RA), D-3 and RA, or solvent control. Growth inhibitory effects, neurite extension, acetylc holinesterase activity, invasiveness, motility, and N-myc protein expr ession were examined following treatment. Results: Growth inhibition w as observed at concentrations of >24 nM. D-3 stimulated the differenti ation of LA-N-5 cells as demonstrated by increased neurite outgrowth, increased acetylcholinesterase activity, and decreased invasiveness. A decrease in N-myc expression was observed in immunostained cells trea ted with either agent alone, with a more profound effect appreciated w ith the combination. Conclusion: Vitamin D-3 decreases N-myc expressio n in LA-N-5 human neuroblastoma cells, with extended treatment causing growth inhibition and differentiation. When used in combination with RA, these effects are more profound than with either agent alone. The therapeutic use of differentiating agent combinations such as D-3 and RA may provide a relatively nontoxic means of treating susceptible tum or types.