Taxol inhibits osteoclastic bone resorption.
We have examined the effect of the anti-tumor compound taxol, on osteoclastic bone resorption. In the bone slice assay, taxol (0.1-0.001 microM) dose-dependently inhibited bone resorption with an IC50 of 0.08 microM. Osteoclast survival on bone slices was unaffected by 0.01-1 microM taxol, but 10 microM was cytotoxic. Taxol (1 microM) also inhibited osteoclast spreading (45%) on fibronectin-coated slides. The antiproliferative effects of taxol are due to its unique ability to stabilize microtubules. Primary osteoclasts are nonproliferating end cells, so taxol probably inhibits bone resorption by interfering with other microtubule-dependent functions such as cell polarization, motility or vesicle exocytosis. Since these inhibitory effects on osteoclasts in vitro are seen with therapeutically relevant concentrations, taxol therapy may have beneficial side-effects e.g. inhibition of hypercalcemia and bone metastases.
Hall
T J
TJ
Ciba-Geigy Ltd., Research Department, Basel, Switzerland.
Jeker
H
H
Schaueblin
M
M
D000818:Animals; D000831:Animals, Newborn; D001862:Bone Resorption / Q000188:drug therapy*; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D005269:Femur / Q000166:cytology; D010006:Osteoblasts / Q000166:cytology / Q000187:drug effects*; D017239:Paclitaxel / Q000627:therapeutic use*; D051381:Rats; D013977:Tibia / Q000166:cytology
D017239:Paclitaxel