Accession Number : ADA415608


Title :   Chemomodulation of Doxorubicin Pharmacodynamics


Descriptive Note : Annual rept. 30 Sep 2001-29 Sep 2002


Corporate Author : HOWARD UNIV WASHINGTON DC


Personal Author(s) : Sridhar, Rajagopalan


Full Text : https://apps.dtic.mil/dtic/tr/fulltext/u2/a415608.pdf


Report Date : Oct 2002


Pagination or Media Count : 39


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.


Descriptors :   *PHARMACOLOGY , *BREAST CANCER , SOURCES , TOXICITY , LIPIDS , PROTEINS , AMINES , RELIABILITY , OXIDATION , MODULATION , CELLS(BIOLOGY) , WILDLIFE , HEART , CHEMOTHERAPY , MICROSOMES , DRUG TOLERANCE , PHOSPHORUS TRANSFERASES , NICOTINE


Subject Categories : Anatomy and Physiology
      Medicine and Medical Research


Distribution Statement : APPROVED FOR PUBLIC RELEASE