Microtubule-active drugs suppress the closure of the permeability transition pore in tumour mitochondria.
We report the effects of anticancer drugs, inhibitors of microtubule organisation, on the mitochondrial permeability transition pore (PTP) in Ehrlich ascites tumour cells. Taxol (5-20 microM) and colchicine (100-500 microM) prevented closing of the cyclosporin A-sensitive PTP. No taxol or colchicine effects on oxidative phosphorylation were observed in the range of concentrations used. We suggest that either membrane-bound tubulin per se can be part of PTP and/or the attachment of mitochondria to the microtubular network is essential for PTP regulation. The taxol inhibition of PTP closure, mediated through interaction with the cytoskeleton, sheds new light on the cytotoxic properties of this anticancer drug.
Evtodienko
Y V
YV
Institute of Theoretical and Experimental Biophysics, Pushchino, Russian Federation.
Teplova
V V
VV
Sidash
S S
SS
Ichas
F
F
Mazat
J P
JP
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism*; D002286:Carcinoma, Ehrlich Tumor / Q000378:metabolism*; D003078:Colchicine / Q000494:pharmacology*; D016572:Cyclosporine / Q000494:pharmacology; D007425:Intracellular Membranes / Q000187:drug effects* / Q000378:metabolism; D051379:Mice; D008870:Microtubules / Q000187:drug effects / Q000378:metabolism; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism; D017239:Paclitaxel / Q000494:pharmacology*; D010539:Permeability / Q000187:drug effects
D000970:Antineoplastic Agents; D016572:Cyclosporine; D017239:Paclitaxel; D003078:Colchicine; D002118:Calcium