Sildenafil and Phosphodiesterase-5 Inhibitors to Reduce Cardiotoxicity and Enhance the Response of Breast Tumor Cells to Doxorubicin
Abstract
In the current work, we report that sildenafil does not protect breast tumor cells from adriamycin based on multiple assays (viable cell number, clonogenic survival, cell cycle distribution and DNA damage). Furthermore, clonogenic survival assays support the conclusion that sildenafil sensitizes breast tumor cells lacking functional p53 to Adriamycin. Since breast cancer frequently is shown to express mutant p53, these findings support the potential utility of sildenafil as a cardioprotectant that is unlikely to interfere with the antitumor actions of Adriamycin (or other chemotherapeutic agents; see previous report). Sildenafil does not increase Adriamycin toxicity to bone marrow cells or macrophages. Again, these findings indicate that sildenafil is unlikely to increase host toxicity of Adriamycin. Adriamycin has the capacity to produce multiple modes of cell death in the breast tumor cells. We now have evidence that Adriamycin also functions through the generation of free radicals to promote senescence. These findings raise questions relating to the selectivity of Adriamycin against the tumor cell versus the heart that require further exploration.
Document Details
- Document Type
- Technical Report
- Publication Date
- Mar 01, 2009
- Accession Number
- ADA548197
Entities
People
- David A. Gewirtz
Organizations
- Virginia Commonwealth University