Beta-Adrenergic Receptors Regulating Growth and Replication of Breast Cancer Cells: Basic and Therapeutic Implications
Abstract
This study explores beta-adrenoceptors on breast cancer cells as a therapeutic target. MDA-MB-23 1 human breast cancer cells express high beta2-adrenoceptor levels that are linked to inhibition of mitosis through the production of cyclic AMP. The phosphodiesterase inhibitor, theophylline, reduced cell number and altered cellular morphology. In the current year, we evaluated the evaluated the effects of theophylline on macromolecule synthesis and indices of cell viability. Theophylline evoked a concentration- and time-dependent decrease in DNA synthesis. However, the decrease in cell number was greater than that predicted from mitotic arrest. Assessment of protein synthesis indicated a second effect separable from that on DNA synthesis; this was confirmed by decreased cell viability and adhesion. Exposure to the phosphodiesterase inhibitor, IBMX, in concentrations that produced inhibition of DNA synthesis equivalent to that seen with theophylline, elicited a smaller reduction in cell number. Theophylline also evoked specific changes in the expression or function of membrane-bound adenylyl cyclase activity, effects that are likely to contribute to sustained reactivity of these cells to other cAMP-related inhibitors of cell proliferation, such as isoproterenol. The multiple pharmacologic properties of theophylline, producing mitotic inhibition, cytotoxicity and altered signaling in MDA-MB-23 1 cells provide insight ht into novel therapeutic strategies.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jul 01, 2000
- Accession Number
- ADB266157
Entities
People
- Theodore Slotkin
Organizations
- Duke University Hospital