Doxorubicin is a potent inhibitor of interleukin 1 induced cartilage proteoglycan resorption in-vitro.
Since interleukin 1 (IL-1) induces the transcriptional synthesis of enzymes responsible for cartilage resorption it was decided to examine the effects of the antitumour drug, doxorubicin, a DNA transcriptional inhibitor, on alpha IL-1-induced cartilage--resorption in-vitro. Doxorubicin inhibited the resorption in a concentration-dependent fashion, an effect which was shown to be reversible. Fine structure of the chondrocytes was preserved by the doxorubicin treatment with IL-1 in contrast to the extensive cellular destruction evident in cartilage treated with IL-1 alone. [14C]doxorubicin was bound to cartilage proteoglycans, and this effect was promoted by treatment of the cartilage with IL-1. This binding of the drug may prevent access of the proteoglycans to destructive enzymes during the resorptive process induced by IL-1.
Rainsford
K D
KD
Anti-inflammatory Research Unit, Strangeways Research Laboratory, Cambridge, UK.
D000818:Animals; D002356:Cartilage / Q000187:drug effects / Q000378:metabolism*; D002417:Cattle; D003609:Dactinomycin / Q000494:pharmacology; D004317:Doxorubicin / Q000494:pharmacology*; D066298:In Vitro Techniques; D007375:Interleukin-1 / Q000037:antagonists & inhibitors*; D008854:Microscopy, Electron; D011509:Proteoglycans / Q000378:metabolism*; D013552:Swine
D007375:Interleukin-1; D011509:Proteoglycans; D003609:Dactinomycin; D004317:Doxorubicin