title: Interference with actin dynamics is superior to disturbance of microtubule function in the inhibition of human ovarian cancer cell motility.
abstract: Cellular movement is mainly orchestrated by the actin and microtubule cytoskeleton in which Rho GTPases closely collaborate. We studied whether cytoskeleton-interfering agents at subtoxic and 50% growth-inhibiting concentrations affect motility of five unselected human ovarian cancer cell lines. Cisplatin and doxorubicin as control cytotoxic agents were not effective, the microtubule-targeting agents docetaxel, epothilone B and vinblastine only marginally inhibited cell motility, while the actin-targeting agent cytochalasin D was most potent in hampering both cell migration and invasion. Disturbance of microtubule dynamics by docetaxel did not importantly affect the cellular structures of beta-tubulin and F-actin. In contrast, hindrance of actin dynamics by cytochalasin D resulted in loss of lamellipodial extensions, induced thick layers of F-actin and disorder in cellular organization. In OVCAR-3 cells the activity of Rac1 was only slightly diminished by docetaxel, but clearly reduced by cytochalasin D. In conclusion, targeting the actin cytoskeleton might provide a means to prevent metastasis formation.
authors.affiliation: Department of Medical Oncology, VU University Medical Center, De Boelelaan 1117, 1081 HV Amsterdam, The Netherlands.
authors.forename: Marcel N A
authors.initials: MN
authors.lastname: Bijman
authors.forename: Maria P A
authors.initials: MP
authors.lastname: van Berkel
authors.forename: Geerten P
authors.initials: GP
authors.lastname: van Nieuw Amerongen
authors.forename: Epie
authors.initials: E
authors.lastname: Boven
mesh_terms: D000199:Actins / Q000037:antagonists & inhibitors* / Q000502:physiology*; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects / Q000502:physiology*; D003599:Cytoskeleton / Q000187:drug effects / Q000502:physiology; D005260:Female; D006801:Humans; D008870:Microtubules / Q000187:drug effects / Q000502:physiology*; D010051:Ovarian Neoplasms / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology*
chemical_list: D000199:Actins; D000970:Antineoplastic Agents