The vitamin D-3 analog EB 1089 enhances the antiproliferative and apoptotic effects of adriamycin in MCF-7 breast tumor cells

Exposure of MCF-7 breast tumor cells to the vitamin D-3 analog, EB 1089 enh ances the response to adriamycin. Clonogenic survival studies indicate that EB 1089 shifts the dose-response curve for sensitivity to adriamycin by ap proximately six-fold in p53 wild-type MCF-7 cells; comparative studies in M CF-7 cells with a temperature-sensitive dominant negative p53 mutation show less than a two-fold shift in adriamycin sensitivity in the presence of EB 1089. The combination of EB 1089 with adriamycin also promotes apoptotic c ell death in the p53 wild-type MCF-7 cells but not in the MCF-7 cells expre ssing mutant p53. EB 1089 treatment blocks the increase in p21(waf1/cip1) l evels induced by adriamycin and interferes with induction of MAP kinase act ivity by ionizing radiation, effects which could be related to the capacity of EB 1089 to promote secretion of insulin-like growth factor binding prot ein. Taken together with our previous findings that EB 1089 enhances breast tumor cell sensitivity to ionizing radiation, there studies further suppor t the concept that vitamin D-3 analogs could have utility in combination wi th conventional chemotherapy and/or radiotherapy in the treatment of breast cancer.