Interaction of geiparvarin and related compounds with purified microtubular protein.
Geiparvarin is an antiproliferative compound whose mechanism of action has not yet been identified. We have investigated the biochemical action on purified microtubular protein, as well as on tubulin, of geiparvarin and of some derivatives resulting from its conjugation with two synthetic oestrogens, diethylstilboestrol and meso-hexoestrol, in comparison with the antimicrotubular action of the reference oestrogens. Geiparvarin and derivatives did not inhibit colchicine binding to tubulin nor did they significantly influence GTP-induced polymerization. On the contrary, they effectively counteracted the stimulating effect of taxol on microtubule formation, both in the presence and in the absence of microtubule-associated proteins. A competitive inhibition mechanism at the taxol binding site of tubulin may thus be proposed to explain the antimicrotubular action of geiparvarin.
Miglietta
A
A
Department of Experimental Medicine and Oncology, University of Torino, Italy.
Bocca
C
C
Gadoni
E
E
Gabriel
L
L
Rampa
A
A
Bisi
A
A
Valenti
P
P
Da Re
P
P
D000818:Animals; D001667:Binding, Competitive; D001921:Brain; D002417:Cattle; D003078:Colchicine / Q000737:chemistry; D003374:Coumarins / Q000737:chemistry / Q000494:pharmacology*; D004054:Diethylstilbestrol / Q000737:chemistry; D006131:Growth Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D006160:Guanosine Triphosphate / Q000737:chemistry; D008870:Microtubules / Q000187:drug effects*; D017239:Paclitaxel / Q000737:chemistry; D014404:Tubulin / Q000737:chemistry
D003374:Coumarins; D006131:Growth Inhibitors; D014404:Tubulin; D004054:Diethylstilbestrol; D006160:Guanosine Triphosphate; C058446:geiparvarin; D017239:Paclitaxel; D003078:Colchicine