Interference with actin dynamics is superior to disturbance of microtubule function in the inhibition of human ovarian cancer cell motility.
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.
Bijman
Marcel N A
MN
Department of Medical Oncology, VU University Medical Center, De Boelelaan 1117, 1081 HV Amsterdam, The Netherlands.
van Berkel
Maria P A
MP
van Nieuw Amerongen
Geerten P
GP
Boven
Epie
E
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*
D000199:Actins; D000970:Antineoplastic Agents