title: Comparative effects of 4-phenyl-3-butenoic acid and vorinostat on cell growth and signaling.
abstract: OBJECTIVE
  4-phenyl-3-butenoic acid (PBA) is a small-molecule anti-inflammatory agent, which has been shown to inhibit growth, increase gap junction intercellular communication and modulate activation of p38 mitogen-activated protein kinase (p38 MAPK) and c-jun n-terminal kinase (JNK) in tumorigenic cells at concentrations that do not similarly affect non-tumorigenic cells. Vorinostat is an anticancer agent structurally similar to PBA. The purpose of this study was to compare the effects of these two agents on JNK and p38 activation, cell growth and gap junction intercellular communication (GJIC).
  
  
  METHODS
  Cell growth, GJIC and western blot analyses were performed utilizing tumorigenic WBras1 and H2009 human carcinoma cells, and non-tumorigenic WBneo3 and human bronchial epithelial (HBE) cells.
  
  
  RESULTS
  Both compounds significantly inhibited WBras1 and H2009 tumorigenic cell growth and increased GJIC in WBras1 cells, as previously reported for PBA. Under similar conditions, both compounds increased phosphorylation of p38 MAPK in tumorigenic but not in non-tumorigenic cells and decreased phosphorylation of JNK in tumorigenic cells. However, a decrease in phosphorylation of JNK occurred in non-tumorigenic WBras1 cells following vorinostat treatment but not PBA treatment. Both compounds showed a selective growth inhibition of H2009 human carcinoma over normal HBE lung cells but, unlike PBA, vorinostat significantly decreased cell growth in WBneo3 cells.
  
  
  CONCLUSIONS
  Overall, PBA exhibited similar effects to vorinostat in tumorigenic cells, while also showing reduced effects on JNK phosphorylation and growth in non-tumorigenic cells compared to ras-transformed cells.
authors: Department of Pharmaceutical Sciences, College of Pharmacy, Mercer University, Atlanta, GA, U.S.A.
authors: Timothy J
authors: TJ
authors: Burns
authors: Department of Pharmaceutical Sciences, College of Pharmacy, Mercer University, Atlanta, GA, U.S.A.
authors: Amna
authors: A
authors: Ali
authors: Department of Pharmaceutical Sciences, College of Pharmacy, Mercer University, Atlanta, GA, U.S.A. matesic_df@mercer.edu.
authors: Diane F
authors: DF
authors: Matesic
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D002455:Cell Division / Q000187:drug effects*; D002460:Cell Line; D005229:Fatty Acids, Monounsaturated / Q000494:pharmacology*; D006877:Hydroxamic Acids / Q000494:pharmacology*; D008099:Liver / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D048670:MAP Kinase Kinase 4 / Q000378:metabolism; D010766:Phosphorylation; D051381:Rats; D011916:Rats, Inbred F344; D015398:Signal Transduction / Q000187:drug effects*; D000077337:Vorinostat
chemical_list: D000970:Antineoplastic Agents; D005229:Fatty Acids, Monounsaturated; D006877:Hydroxamic Acids; C064180:4-phenyl-3-butenoic acid; D000077337:Vorinostat; D048670:MAP Kinase Kinase 4
keywords: JNK; PBA; gap junction; p38 MAPK; vorinostat