title: T0901317 inhibits cisplatin-induced apoptosis in ovarian cancer cells [corrected].
abstract: OBJECTIVE
  To determine the function of T0901317 in combination treatment with cisplatin in ovarian cancer cells.
  
  
  METHODS
  We screened the effects of 3 nuclear hormone receptor ligands on cell viability in a panel of ovarian cancer cell lines. T0901317 regulation of apoptosis and cell cycle regulators was determined when applied as a single agent or in combination with cisplatin.
  
  
  RESULTS
  Surprisingly, the liver X receptor agonist T0901317 had no significant effects on a panel of 7 ovarian cancer cell lines as a single agent. T0901317 does, however, significantly decrease cisplatin efficacy in at least 3 ovarian cancer cell lines. T0901317 reduces cisplatin-induced apoptosis and reverses cisplatin-induced expression of cell cycle regulators. T0901317 seems to work in a liver X receptor-, pregnane X receptor-, and farnesoid X receptor-independent manner, as agonists of these nuclear hormone receptors did not show similar effects. Interestingly, in the A2780-cp drug-resistant cell line, the effect of T0901317 is lost, suggesting that the pathways stimulated by T0901317 to reduce cisplatin efficacy could be inherently active features of the selected resistance.
  
  
  CONCLUSIONS
  Together, these data suggest that T0901317 inhibits cisplatin in some ovarian cancer cells. These data provide an avenue to investigate when T0901317 may be acting to promote tumor survival and drug resistance through control of apoptosis and when it may be acting as an antitumor agent as has been previously reported.
authors.affiliation: Department of Molecular Biology, Cell Biology, and Biochemistry, Brown University, Providence, RI, USA.
authors.forename: Daniel H
authors.initials: DH
authors.lastname: Miller
authors.forename: Andrew K
authors.initials: AK
authors.lastname: Fischer
authors.forename: Katrina F
authors.initials: KF
authors.lastname: Chu
authors.forename: Risa
authors.initials: R
authors.lastname: Burr
authors.forename: Sara
authors.initials: S
authors.lastname: Hillenmeyer
authors.forename: Laurent
authors.initials: L
authors.lastname: Brard
authors.forename: Alexander S
authors.initials: AS
authors.lastname: Brodsky
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects*; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D002945:Cisplatin / Q000494:pharmacology / Q000627:therapeutic use*; D004336:Drug Antagonism; D004354:Drug Screening Assays, Antitumor; D005260:Female; D006801:Humans; D006845:Hydrocarbons, Fluorinated / Q000494:pharmacology*; D000071518:Liver X Receptors; D057093:Orphan Nuclear Receptors / Q000819:agonists*; D010051:Ovarian Neoplasms / Q000188:drug therapy*; D013449:Sulfonamides / Q000494:pharmacology*; D005466:Fluorocarbons; D000096926:Benzenesulfonamides
chemical_list: D000970:Antineoplastic Agents; D002945:Cisplatin; D006845:Hydrocarbons, Fluorinated; D000071518:Liver X Receptors; D057093:Orphan Nuclear Receptors; D013449:Sulfonamides; C423915:T0901317; D005466:Fluorocarbons; D000096926:Benzenesulfonamides