title: Effect of novobiocin on the viability of human gingival fibroblasts (HGF-1).
abstract: BACKGROUND
  Novobiocin is a coumarin antibiotic, which affects also eukaryotic cells inhibiting activity of Heat shock protein 90 (Hsp90). The Hsp90 represents a molecular chaperone critical for stabilization and activation of many proteins, particularly oncoproteins that drive cancer progression. Currently, Hsp90 inhibitors focus a significant attention since they form a potentially new class of drugs in therapy of cancer. However, in the process of tumorigenesis a significant role is played also by the microenvironment of the tumour, and, in particular, by cancer-associated fibroblasts (CAFs). This study aimed at examination of the effect played by novobiocin on viability of human gingival fibroblasts (HGF-1).
  
  
  METHODS
  The studies were conducted using 24 h cultures of human gingival fibroblasts - HGF-1 (CRL-2014) in Chamber Slides, in presence of 0.1, 0.5, 1.0, 2.5 or 5.0 mM novobiocin. Cell viability was evaluated using fluorescence test, ATP assay and LDH release.
  
  
  RESULTS
  Viability of HGF-1 was drastically reduced after 5 hour treatment with novobiocin in concentrations of 1 mM or higher. In turn, the percentage of LDH-releasing cells after 5 h did not differ from control value although it significantly increased after 10 h incubation with 1 mM and continued to increase till the 20th hour.
  
  
  CONCLUSIONS
  The obtained data indicate that novobiocin may induce death of human gingival fibroblasts. Therefore, application of the Hsp90 inhibitor in neoplastic therapy seems controversial: on one hand novobiocin reduces tumour-associated CAFs but, on the other, it may induce a significant destruction of periodontium.
authors.forename: Anna K
authors.initials: AK
authors.lastname: Szkaradkiewicz
authors.affiliation: Department of Medical Microbiology, University of Medical Sciences, Wieniawskiego 3, str,, 61-712 Poznań, Poland. tkarpin@interia.pl.
authors.forename: Tomasz M
authors.initials: TM
authors.lastname: Karpiński
authors.forename: Andrzej
authors.initials: A
authors.lastname: Szkaradkiewicz
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000494:pharmacology*; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D005347:Fibroblasts / Q000187:drug effects*; D005881:Gingiva / Q000166:cytology; D018841:HSP90 Heat-Shock Proteins / Q000037:antagonists & inhibitors*; D006801:Humans; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D009675:Novobiocin / Q000494:pharmacology*
chemical_list: D000900:Anti-Bacterial Agents; D000970:Antineoplastic Agents; D018841:HSP90 Heat-Shock Proteins; D009675:Novobiocin; D000255:Adenosine Triphosphate; D007770:L-Lactate Dehydrogenase