Antiangiogenic Action of Chemically Modified Tetracyclines in Breast Cancer
Abstract
The long term objective of this project is to evaluate the capacity of a group of nonantimicrobial chemically modified tetracyclines (CMTs) to downregulate the angiogenic response which maintains breast tumor growth and proliferation. In this first year we determined levels of the angiogenic factor VEGF released by two breast tumor cell lines, MCF-7 and MDA-MB-23 1 and demonstrated dose-dependent inhibition of VEGF release from both cell lines cultured for 24 hours with CMT-3 or CMT-308. CMT-308 was the more potent inhibitor of the two CMTs at all doses. Neither CMT was cytotoxic to either cell line at doses which can be achieved in patients. Addition of the growth factor TGF-p to either cell line resulted in factor-dose-dependent increases in levels of released VEGF, but the augmented VEGF levels could be diminished somewhat by CMT-3 and more significantly by CMT-308. VEGF levels released by either cell line were unaffected by IGF-l. The human monocytoid line Mono Mac 6 also released VEGF in the absence of added stimuli; VEGF levels from Mono Mac 6 were not affected by TGF-beta or IGF- 1, but were diminished somewhat in the presence of CMT-3 and markedly (to virtually undetectable levels) in the presence of CMT-308. CMT-3 and CMT-308 were not cytotoxic to confluent human umbilical vein endothelial cells at doses which inhibited VEGF release from the breast tumor cell lines and Mono Mac 6 cells. These results suggest that CMTs, especially CMT-308, may be of use as antiangiogenic agents in management of breast cancer.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jun 01, 2002
- Accession Number
- ADA407391
Entities
People
- Sanford R. Simon
Organizations
- State University of New York