Antimicrotubular and cytotoxic activity of geiparvarin analogues, alone and in combination with paclitaxel.
Geiparvarin is an antiproliferative compound isolated from the leaves of Geijera parviflora, and may represent a new drug which targets tubulin. To better explore the potential use of this agent, we investigated the antimicrotubular and cytotoxic effects of new synthetic aromatic derivatives of geiparvarin. These drugs inhibited polymerization of microtubular protein, particularly when the assembly was induced by paclitaxel. The microtubular network organization of fibroblasts was altered more effectively by some drugs. Normal microtubule architecture completely disappeared when the cells were treated simultaneously with drugs and paclitaxel: microtubules depolymerized or were reorganized into bundles, in a similar but more disarrayed fashion than that observed after treatment with paclitaxel alone. Cytotoxicity studies showed a dose-dependent effect, whereas combined administration of drugs and paclitaxel increased cytotoxicity, more effectively in paclitaxel versus derivatives administration alone.
Miglietta
A
A
Department of Experimental Medicine and Oncology, University of Torino, Corso Raffaello 30, 10125 Torino, Italy. antonella.miglietta@unito.it
Bocca
C
C
Gabriel
L
L
Rampa
A
A
Bisi
A
A
Valenti
P
P
D016475:3T3 Cells; D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology*; D002455:Cell Division / Q000187:drug effects; D003374:Coumarins / Q000494:pharmacology*; D003599:Cytoskeleton / Q000187:drug effects; D006131:Growth Inhibitors / Q000737:chemistry; D051379:Mice; D008807:Mice, Inbred BALB C; D008870:Microtubules / Q000187:drug effects*; D017239:Paclitaxel / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D014404:Tubulin / Q000737:chemistry / Q000187:drug effects*
D000972:Antineoplastic Agents, Phytogenic; D003374:Coumarins; D006131:Growth Inhibitors; D014404:Tubulin; C058446:geiparvarin; D017239:Paclitaxel