GEIPARVARIN AND DERIVATIVES IN COMBINATION WITH TAXOL - EFFECT ON MICROTUBULAR ORGANIZATION IN 3T3 FIBROBLASTS

Geiparvarin, a natural product that exhibits antiproliferative activit y, inhibits the growth of various tumour cell lines with a mechanism o f action so far unknown. Our preliminary findings showed that geiparva rin and some derivatives obtained from its conjugation with diethylsti lboestrol and meso-hexestrol significantly inhibit taxol-induced in vi tro polymerization of both tubulin and microtubular protein. In this s tudy we investigated the effect of geiparvarin and of the oestrogen-co mbined derivatives on the cellular microtubular network of fibroblasts . Geiparvarin altered the microtubular organization of fibroblasts and strengthened the derangement of the microtubular pattern in cells exp osed simultaneously to taxol. However, the microtubular network remain ed quite well organized in fibroblasts exposed to geiparvarin and prei ncubated with taxol, which in this case prevented the deranging effect of the former. The antimicrotubular activity of the oestrogen-combine d derivatives was more similar to that of geiparvarin than to that of the oestrogens, and often this activity was stronger than that of each reference drug alone; the cytotoxic activity examined in the same exp erimental conditions generally confirmed the microscopic analysis.