Enhancement of Breast Cancer Therapy by 6-Aminonicotinamide
Abstract
This work was undertaken to determine if 6-aminonicotiamide (6AN) can enhance efficacy of radiation (XRT) and/or chemotherapy (paclitaxel or adriamycin). The study was done in hormone resistant (MDA-MB-435) and hormone sensitive (MCF-7) breast tumors. The interval between 6AN and XRT/chemotherapy was determined by 31P NMR spectral changes. Spectral changes were noted post 6AN in perfused MCF-7 and MDA-MB-435 cells including a decrease in the ratio of phosphocreatine to inorganic phosphate (Pi) and an increase in 6-phosphogluconate (a product of the pentose phosphate pathway) to Pi. Similar changes were noted in vivo in the MCF-7. 6AN enhanced the effect of XRT (2 Gy) and adriamycin in the MCF-7 but inhibited the effect of paclitaxel. In the MDA-MP-435, no enhancement was noted in vitro. In vivo, 6AN enhanced the effect of radiation (5Gy/fraction) and adriamycin in the MCF-7. Treatment with paclitaxel was too toxic with SAN to evaluate. In the MDA-MB-435, enhancement of XRT was noted with 6AN, but not of adriamycin. The latter may have been to a lower dose of adriamycin (5mg/kg) than was used in the MCF-7. 6AN inhibited paclitaxel in the MDA-MB-435. 6AN was effective at non-toxic doses in enhancing the effect of XPT in both MCP-7 and MDA-MB-435, but inhibited paclitaxel in the latter tumors.
Document Details
- Document Type
- Technical Report
- Publication Date
- May 01, 2002
- Accession Number
- ADA409633
Entities
People
- Jason A Koutcher
Organizations
- Memorial Sloan Kettering Cancer Center