title: Valproic acid, but not levetiracetam, selectively decreases HDAC7 and HDAC2 expression in human ovarian cancer cells.
abstract: Histone deacetylases (HDACs) are often overexpressed in cancer cells, leading to altered expression and activity of numerous proteins involved in carcinogenesis. Recent evidence suggests that expression of class I HDACs is increased in ovarian carcinomas and plays a significant role in carcinogenesis and resistance to chemotherapeutic agents. Two compounds, valproic acid (VPA) and levetiracetam (LEV), exhibit HDAC inhibitor (HDACI) activity in various cell types, but data concerning their activity in ovarian cancer are lacking. Here we compared the effects of VPA and LEV as HDACIs, using a human ovarian cancer cell line, OVCAR-3. Cells were cultured with VPA or LEV at concentrations between 1 and 10 mM for 1-24h. HDAC activity was determined by fluorometric assay and confirmed by western blotting. Expression of HDAC genes was determined by real-time PCR and HDAC proteins expression was evaluated by western blotting. Additionally, we used high-performance liquid chromatography to determine whether OVCAR-3 cells can metabolize LEV to its major metabolite, 2-pyrrolidinone-n-butyric acid (PBA), which might exert HDACI activity. LEV, however, had no apparent effect on HDAC activity, or gene and protein expression. The OVCAR-3 cell line was able to metabolize LEV to PBA, but the effect was small. Our observations suggest that VPA should be considered as a possible adjunctive drug in ovarian cancer treatment.
authors.affiliation: Department of Physiology and Toxicology of Reproduction, Chair of Animal Physiology, Institute of Zoology, Jagiellonian University, Cracow, Poland. Electronic address: patrycja.kwiecinska@uj.edu.pl.
authors.forename: Patrycja
authors.initials: P
authors.lastname: Kwiecińska
authors.forename: Anna
authors.initials: A
authors.lastname: Wróbel
authors.forename: Erik
authors.initials: E
authors.lastname: Taubøll
authors.forename: Ewa Łucja
authors.initials: EŁ
authors.lastname: Gregoraszczuk
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology; D045744:Cell Line, Tumor; D005260:Female; D056464:Histone Deacetylase 2 / Q000235:genetics / Q000378:metabolism*; D056572:Histone Deacetylase Inhibitors / Q000494:pharmacology*; D006655:Histone Deacetylases / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D000077287:Levetiracetam; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology; D010889:Piracetam / Q000031:analogs & derivatives* / Q000494:pharmacology; D014635:Valproic Acid / Q000494:pharmacology*
chemical_list: D000970:Antineoplastic Agents; D056572:Histone Deacetylase Inhibitors; D000077287:Levetiracetam; D014635:Valproic Acid; C533423:HDAC2 protein, human; C543273:HDAC7 protein, human; D056464:Histone Deacetylase 2; D006655:Histone Deacetylases; D010889:Piracetam
keywords: Histone deacetylases; Levetiracetam; Ovarian cancer cell line OVCAR-3; Valproic acid