'Rings' of F-actin form around the nucleus in cultured human MCF7 adenocarcinoma cells upon exposure to both taxol and taxotere

The anti-cancer taxoids, Taxol(R) (paclitaxel) and Taxotere(R) (docetaxel), are the most promising anti-mitotic agents developed for cancer treatment in the past decade. The effectiveness of this new class of compounds lies i n their unique mechanism of action on the cytoskeleton. Both taxol and taxo tere bind to microtubules and shift the normal equilibrium between monomeri c and polymerized tubulin to favor the polymerized form by strongly promoti ng tubulin assembly and inhibiting microtubule depolymerization. Although V ery similar in structure, these two compounds have recently demonstrated di fferent in vitro, in vivo, and clinical activities; however, no study to da te has effectively compared specific cytoskeletal alterations induced by ta xol and taxotere in cultured cells. Using specific staining techniques for both F-actin and alpha-tubulin, this study provides the first detailed immu nohistochemical comparison of the effects of equimolar concentrations of ta xol and taxotere on both the microfilament and microtubule networks in a cu ltured cell line. Using human MCF7 breast adenocarcinoma cells, new observa tions of taxotere/taxol alterations of the cytoskeleton include: an increas ed abundance of parallel microtubule 'bundles' in taxotere treated cells an d a definitive reorganization of the microfilament network which results in novel ring-like formations of F-actin condensed exclusively in the perinuc lear zone. Reorganization of the actin cytoskeleton induced by a taxoid dis ruption of the microtubule equilibrium is indicative of the interdependence between microtubules and microfilaments in this transformed cell line and suggests that the indirect role of the taxoids on the microfilament network may have been overlooked in their mechanism of action as chemotherapeutic agents. (C) 2000 Elsevier Science Inc. All rights reserved.