Chemomodulation of Doxorubicin Pharmacodynamics
Abstract
The wild type MCF7 human breast cancer cells and the multidrug resistant cell line designated as MCF7/ADR are reported to be genetically unrelated. Our attempts to produce stable multidrug resistant mutants from MCF7 were unsuccessful. However, we found reliable sources of wild type and related multidrug resistant breast cancer cell lines. This has further delayed our experiments. We are in the process of repeating our experiments with these genetically related cell lines. Both dipyridamole and raloxifene resembled tamoxifen in potentiating the cytotoxicity of doxorubicin towards MCF7/ADR cells, and inhibiting doxorubicin mediated microsomal lipid peroxidation. Raloxifene, dipyridamole and tamoxifen can inhibit protein kinase C, which is an attractive target for modulating multidrug resistance. Nicotine, which is cardiotoxic, can activate protein kinase C pathway. Kaloxifene, tamoxifen and dipyridamole have basic amino groups in common, but unlike nicotine, they inhibit protein kinase C and sensitize multidrug resistant cells.
Document Details
- Document Type
- Technical Report
- Publication Date
- Oct 01, 2002
- Accession Number
- ADA415608
Entities
People
- Rajagopalan Sridhar
Organizations
- Howard University