ABSTRACT: The vitamin D3 analog, ILX-23-7553, enhances the response
to Adriamycin and irradiation in MCF-7 breast tumor cells
Ionizing radiation and the anthracycline antibiotic,
Adriamycin, generally fail to promote a primary apoptotic response
in experimental breast tumor cell lines. Similarly, the primary
response of breast tumor cells to vitamin D3 (1,25(OH)2D3) and
vitamin D3 analogs such as EB 1089 is growth inhibition.
studies have demonstrated that pretreatment of MCF-7 breast tumor
cells with vitamin D3 or EB 1089 can increase sensitivity to
both Adriamycin and irradiation. Purpose: The capacity of the
vitamin D3 analog, ILX 23-7553, to enhance the antiproliferative
and cytotoxic effects of Adriamycin or irradiation and to promote
apoptosis in MCF-7 breast tumor cells was assessed in the present
Results: Pretreatment of MCF-7 cells with ILX 23-7553
followed by Adriamycin or irradiation decreased viable cell numbers
by 97% and 93%, respectively. Cell numbers were reduced by 56%,
74% and 75% by ILX 23-7553, Adriamycin and irradiation alone.
Pretreatment with ILX 23-7553 also shifted the dose response
curve for clonogenic survival, increasing sensitivity to Adriamycin
2.5-fold and sensitivity to radiation fourfold. In addition,
ILX 23-7553 pretreatment conferred sensitivity to Adriamycin-
or irradiation-induced DNA fragmentation and resulted in morphological
changes indicative of apoptotic cell death in MCF-7 cells.
analysis demonstrated that ILX 23-7553 interacts additively and
not synergistically with both Adriamycin and irradiation. Conclusions:
ILX 23-7553 enhances the effects of Adriamycin and irradiation
in MCF-7 breast tumor cells by decreasing viable cell numbers,
reducing clonogenic survival and inducing apoptotic cell death.
Current studies are focused on elucidating the mechanisms underlying
the induction of apoptosis as well as understanding the nature
of the interactions between ILX 23-7553 and Adriamycin or irradiation.
Cancer Chemotherapy & Pharmacology, 5/01
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