Effect of the vitamin D3 analog ILX 23-7553 on apoptosis and sensitivity to fractionated radiation in breast tumor cells and normal human fibroblasts Mark K. Polar1, 2, Chris Gennings3, Misook Park3, Mona S. Gupta1, 2 and David A. Gewirtz1, 2 (1) Department of Pharmacology/Toxicology, Medical College of Virginia, Virginia Commonwealth University, P.O. Box 980230, Richmond, VA, USA (2) Department of Medicine, Medical College of Virginia, Virginia Commonwealth University, P.O. Box 980230, Richmond, VA, USA (3) Department of Biostatistics, Medical College of Virginia, Virginia Commonwealth University, P.O. Box 980230, Richmond, VA, USA Abstract Purpose: Previous work from this laboratory has demonstrated that the vitamin D3 analogs EB 1089 and ILX 23-7553 enhance the response of breast tumor cells to ionizing radiation and promote radiation-induced apoptotic cell death. The current studies were designed to more closely simulate clinical radiotherapy in the treatment of breast cancer by examining the utility of ILX 23-7553 as an adjunct to fractionated ionizing radiation. The potential toxicity to normal tissue of the combination of ILX 23-7553 and fractionated radiation was assessed in a model of BJ human fibroblasts in culture. Methods MCF-7 cells and human fibroblasts were treated with fractionated radiation alone (5×2 Gy over 3 days), ILX 23-7553 alone (50 nM) or ILX 23-7553 followed by 5×2 Gy. Viable cell numbers were determined by trypan blue exclusion and apoptosis by the TUNEL assay. A statistical model of additivity was utilized to assess the nature of the interaction between ILX 23-7553 and fractionated radiation. Results Radiation and ILX 23-7553 each alone reduced viable cell numbers by 72±3.1% and 62±4.8%, respectively. Pretreatment with ILX 23-7553 followed by 5×2 Gy reduced viable cell numbers by 93.2±0.7%. The interaction between ILX 23-7553 and fractionated radiation appeared to be additive despite the fact that the combination of ILX 23-7553 and fractionated radiation also promoted a twofold increase in apoptotic cell death. ILX 23-7553 failed to enhance the response to radiation or to promote apoptosis in BJ human foreskin fibroblasts. Conclusions ILX 23-7553 enhanced the antiproliferative and apoptotic effects of fractionated ionizing radiation in MCF-7 breast cancer cells. These effects appeared to be selective in that similar responses were not observed in a model of normal human fibroblasts. Vitamin D3 analogs such as ILX 23-7553 may prove to have utility in combination with conventional radiotherapy of breast cancer as well as other malignancies which are sensitive to vitamin D3. Cancer Chemother Pharmacol. 2003 May;51(5):415-21. Epub 2003 Apr 11. ----- Original Message ----- From: AnnFonfa@aol.com To: gewirtz@hsc.vcu.edu Sent: Friday, May 23, 2003 4:39 PM Subject: Read your abstract on Vit D3 analogs Dear Dr. Gewirtz: Did you experiment at all with actual vitamin D as opposed to analogs? Just wondering. Thanks for your response. Ann F. Dr. Gewirtz responds: "Actually Vitamin D3 also works but it is not as potent as the analogs." ----- Original Message ----- From: AnnFonfa@aol.com To: gewirtz@hsc.vcu.edu Sent: Friday, May 23, 2003 5:44 PM Subject: Re: Read your abstract on Vit D3 analogs In a message dated 5/23/2003 5:20:12 PM Eastern Standard Time, gewirtz@hsc.vcu.edu writes: Actually Vitamin D3 also works but it is not as potent as the analogs. >> But will there be toxicity concerns as there are with Vitamin A analogs and NOT with actual vitamin A? Ann F. Response: "Right. Too much Vitamin D can be toxic." Remember we are NOT Doctors and have NO medical training. This site is like an Encylopedia - there are many pages, many links on many topics. Support our work with any size DONATION - see left side of any page - for how to donate. You can help raise awareness of CAM.