title: The acyl glucuronide metabolite of mycophenolic acid induces tubulin polymerization in vitro.
abstract: OBJECTIVE
  The acyl glucuronide (AcMPAG) of mycophenolic acid (MPA) forms covalent protein adducts and possesses antiproliferative properties independent of IMPDH inhibition. The underlying mechanism is unknown. Disorganized tubulin polymerization prevents cell cycle progression. We investigated whether AcMPAG interacts with tubulin polymerization.
  
  
  METHODS
  AcMPAG (1.0-100 microM) was incubated with bovine tubulin in the presence of GTP. Polymerization was followed at 340 nm. The time until onset and the extent of polymerization were determined. MPA (100 microM), phenolic glucuronide MPAG (100 microM), and paclitaxel (10 microM) served as controls.
  
  
  RESULTS
  MPAG was without effect. The AcMPAG effect on tubulin polymerization was dose dependent and significantly stronger (about 2.5-fold) than that of MPA (n=4; p<0.05), but weaker than paclitaxel.
  
  
  CONCLUSIONS
  MPA and AcMPAG can induce tubulin polymerization in the presence of GTP with AcMPAG being significantly stronger. This property of AcMPAG may contribute to its IMPDH independent antiproliferative effect.
authors.affiliation: Zentralinstitut für Klinische Chemie und Laboratoriumsmedizin, Klinikum Stuttgart, Stuttgart, Germany.
authors.forename: Horst
authors.initials: H
authors.lastname: Feichtiger
authors.forename: Eberhard
authors.initials: E
authors.lastname: Wieland
authors.forename: Victor W
authors.initials: VW
authors.lastname: Armstrong
authors.forename: Maria
authors.initials: M
authors.lastname: Shipkova
mesh_terms: D000818:Animals; D002417:Cattle; D004791:Enzyme Inhibitors / Q000378:metabolism*; D020719:Glucuronides / Q000378:metabolism*; D006160:Guanosine Triphosphate / Q000378:metabolism; D009173:Mycophenolic Acid / Q000378:metabolism*; D017239:Paclitaxel / Q000378:metabolism; D011108:Polymers / Q000737:chemistry / Q000378:metabolism; D020836:Protein Structure, Quaternary; D014404:Tubulin / Q000737:chemistry / Q000378:metabolism; D050257:Tubulin Modulators / Q000378:metabolism*
chemical_list: D004791:Enzyme Inhibitors; D020719:Glucuronides; D011108:Polymers; D014404:Tubulin; D050257:Tubulin Modulators; D006160:Guanosine Triphosphate; D009173:Mycophenolic Acid; D017239:Paclitaxel