EFFECTS OF TAXOTERE ON MURINE AND HUMAN TUMOR-CELL LINES

Taxotere (RP 56976, NSC 628503), an analog of taxol, is an inhibitor of depolymerisation of microtubules and is currently in Phase I clinical trials. Comparisons of the cytotoxicities of Taxotere and taxol have been studied on several murine (P388, SVras) and human cell lines (Calc18, HCT116, T24, N417, KB). Taxotere was found more potent than taxol (1.3-12 fold), a result which could be explained by its higher affinity than taxol for microtubules. In agreement with its postulated mechanism of action, Taxotere is more cytotoxic on proliferating than on non proliferating N417 cells and does not inhibit cellular DNA, RNA and protein synthesis. Taxotere gives partial cross resistance on P-glycoprotein resistant P388/DOX cell line, in contrast to taxol which gives a complete cross resistance. On the other hand, no cross resistances were observed on Calc18/AM and P388/CPT5 cell lines, bearing modified activities of topoisomerase II and topoisomerase I, respectively. These results underline the higher cytotoxic activity of Taxotere compared to taxol, and the lack of cross resistance of that class of agent with the topoisomerase I and II-related multidrug resistance phenotypes. © 1992 Academic Press, Inc.