Direct action by doxycycline against canine osteosarcoma cell proliferation and collagenase (MMP-1) activity in vitro.
BACKGROUND
Matrix metalloproteinases (MMPs) produced by tumor cells disrupt the integrity of the extracellular matrix (ECM). Inhibiting MMPs activity could significantly reduce tumor invasion and metastasis.


METHODS
Canine osteosarcoma (OSA) cells were exposed to doxycycline in vitro to determine whether this chemically modified tetracycline had antiproliferative and anticollagenolytic activity.


RESULTS
Doxycycline significantly reduced cell proliferation in a dose dependent manner. Doxycycline at the doses of 5 and 10 micrograms/ml suppressed cell number 50% and 72%, respectively. Furthermore, doxycycline significantly reduced collagenase activity at the doses of 10 and 20 micrograms/ml by 35% and 50%, respectively. OSA cells did not produce any endogenous collagenase in the culture medium.


CONCLUSIONS
This study has shown that doxycycline at doses greater than 5 micrograms/ml in vitro significantly decreases cell proliferation and collagenase (MMP-1) activity. Prospective studies should be conducted to determine if doxycycline, a chemically modified tetracycline with low systemic toxicity, has specific anti-collagenase activity in vivo. Our studies indicate that canine osteosarcoma represents a suitable model for additional in vitro and in vivo studies.
Cakir
Y
Y
Department of Comparative Medicine, College of Veterinary Medicine, University of Tennessee, Knoxville 37901-1071, USA.
Hahn
K A
KA
D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D002452:Cell Count / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D003094:Collagen / Q000378:metabolism; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D004318:Doxycycline / Q000494:pharmacology*; D004789:Enzyme Activation / Q000187:drug effects; D020781:Matrix Metalloproteinase 1 / Q000378:metabolism*; D012516:Osteosarcoma / Q000201:enzymology* / Q000473:pathology*; D014407:Tumor Cells, Cultured
D000900:Anti-Bacterial Agents; D003094:Collagen; D020781:Matrix Metalloproteinase 1; D004318:Doxycycline