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.