Abstract | UNLABELLED: 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 study. 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. Statistical 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.
|
Authors | M Chaudhry, S Sundaram, C Gennings, H Carter, D A Gewirtz |
Journal | Cancer chemotherapy and pharmacology
(Cancer Chemother Pharmacol)
Vol. 47
Issue 5
Pg. 429-36
(May 2001)
ISSN: 0344-5704 [Print] Germany |
PMID | 11391859
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S.)
|
Chemical References |
- Antineoplastic Agents
- ILX237553
- Cholecalciferol
- Doxorubicin
|
Topics |
- Antineoplastic Agents
(pharmacology)
- Apoptosis
(drug effects, radiation effects)
- Breast Neoplasms
(metabolism)
- Cholecalciferol
(analogs & derivatives, pharmacology)
- Doxorubicin
(pharmacology)
- Drug Synergism
- Female
- Humans
- Tumor Cells, Cultured
(drug effects)
|