title: Microtubules and Actin Cytoskeleton of Cryptococcus neoformans as Targets for Anticancer Agents to Potentiate a Novel Approach for New Antifungals.
abstract: BACKGROUND
  We investigated the targeting of microtubules (MT) and F-actin cytoskeleton (AC) of the human pathogenic yeast Cryptococcus neoformans with agents for cancer therapy, in order to examine whether this yeast cytoskeleton could become a new antifungal target for the inhibition of cell division.
  
  
  METHODS
  Cells treated with 10 cytoskeleton inhibitors in yeast extract peptone dextrose medium were investigated by phase-contrast and fluorescence microscopy, and growth inhibition was estimated by cell counts using a Bürker chamber and measuring absorbance for 6 days.
  
  
  RESULTS
  Docetaxel, paclitaxel, vinblastine sulfate salt, cytochalasin D and chlorpropham [isopropyl N-(3-chlorophenyl) carbamate] did not inhibit proliferation. The MT inhibitors methyl benzimidazole-2-ylcarbamate (BCM), nocodazole, thiabendazole (TBZ) and vincristine (VINC) disrupted MT and inhibited mitoses, but anucleated buds emerged on cells that increased in size, vacuolated and seemed to die after 2 days. The response of the cells to the presence of the actin inhibitor latrunculin A (LA) included the disappearance of actin patches, actin cables and actin rings; this arrested budding and cell division. However, in 3-4 days, resistant budding cells appeared in all 5 inhibitors. Disruption of the MT and AC and inhibition of cell division and budding persisted only when the MT and AC inhibitors were combined, i.e. VINC + LA, BCM + LA or TBZ + LA.
  
  
  CONCLUSIONS
  The MT and AC of C. neoformans are new antifungal targets for the persistent inhibition of cell division by combined F-actin and MT inhibitors.
authors.affiliation: Department of Biology, Faculty of Medicine, Masaryk University, Brno, Czech Republic.
authors.forename: Marie
authors.initials: M
authors.lastname: Kopecká
mesh_terms: D008841:Actin Cytoskeleton / Q000187:drug effects*; D000199:Actins / Q000037:antagonists & inhibitors; D000935:Antifungal Agents / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000494:pharmacology*; D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000494:pharmacology; D002455:Cell Division / Q000187:drug effects; D003455:Cryptococcus neoformans / Q000187:drug effects*; D015195:Drug Design; D006801:Humans; D008856:Microscopy, Fluorescence; D008870:Microtubules / Q000187:drug effects; D053778:Thiazolidines / Q000494:pharmacology
chemical_list: D000199:Actins; D000935:Antifungal Agents; D000970:Antineoplastic Agents; D019086:Bridged Bicyclo Compounds, Heterocyclic; D053778:Thiazolidines; C037067:latrunculin A