Selective endothelial growth inhibition by tetracyclines that inhibit collagenase.
The potential of angiogenesis inhibitors as therapy for human diseases is limited by a lack of clinically available agents. We investigated the mechanism of the anti-angiogenesis effects of minocycline, a commonly used drug, and several derivatives. Endothelial cell proliferation was inhibited by several of these compounds. We found that inhibition was associated with inhibition of collagenase, did not require antibiotic activity, and was not related to cytotoxicity. Other microvessel-associated cells were unaffected. This endothelial antiproliferative effect is a potential mechanism of the anti-angiogenic activity of minocycline.
Guerin
C
C
Department of Neurosurgery, Johns Hopkins University School of Medicine, Baltimore, MD.
Laterra
J
J
Masnyk
T
T
Golub
L M
LM
Brem
H
H
D000818:Animals; D001253:Astrocytes / Q000166:cytology / Q000187:drug effects*; D002417:Cattle; D002455:Cell Division / Q000187:drug effects*; D004247:DNA / Q000096:biosynthesis; D004305:Dose-Response Relationship, Drug; D004318:Doxycycline / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects*; D007700:Kinetics; D061965:Matrix Metalloproteinase Inhibitors; D008911:Minocycline / Q000494:pharmacology; D014176:Protein Biosynthesis; D012160:Retina; D013752:Tetracycline / Q000494:pharmacology; D013754:Tetracyclines / Q000494:pharmacology*
D061965:Matrix Metalloproteinase Inhibitors; D013754:Tetracyclines; D004247:DNA; D013752:Tetracycline; D008911:Minocycline; D004318:Doxycycline