• Farnesol-Induced Apoptosis in Oral Squamous Carcinoma Cells is Mediated by MRP1 Extrusion and Depletion of Intracellular Glutathione

      Intapa, Chaidan; Jabra-Rizk, Mary Ann (2013)
      Farnesol is a key intermediate in the sterol biosynthesis pathway in eukaryotic cells that has exhibited significant anti-cancer and antimicrobial activity. We have shown that farnesol triggers apoptosis in oral squamous carcinoma cells (OSCCs) and in the fungal pathogen Candida albicans via a classical apoptotic process. However, the exact mechanism of farnesol cytotoxicity in eukaryotic cells has not been fully elucidated. In the cell, hydrophobic xenobiotics conjugate with glutathione, an antioxidant crucial for cellular detoxification against damaging compounds. This process results in the formation of glutathione S-conjugates which act as substrates for export by ATP-binding cassette transporters (ABC transporter) and are extruded from the cell. This study was undertaken to validate the hypothesis that farnesol conjugation with intracellular glutathione coupled with multidrug resistance-associated protein 1 (MRP1) - mediated extrusion of glutathione-farnesol conjugates and oxidized glutathione results in total glutathione depletion, oxidative stress and ultimately cell death. The combined findings demonstrated that farnesol exposure resulted in significant decrease in intracellular glutathione levels concomitant with intracellular Reactive oxygen species (ROS) accumulation and decrease in cell viability. However, addition of exogenous glutathione maintained intracellular levels and enhanced cell viability. Furthermore, gene and protein expression studies demonstrated significant up-regulation of MRP1 in cells treated with farnesol. However, MRP1 blocking and monoclonal antibody specific inhibition of MRP1 enhanced cell tolerance to farnesol. This is the first study describing the involvement of MRP1-mediated glutathione efflux as a mechanism for farnesol-induced apoptosis in OSCCs. Understanding of the mechanisms underlying farnesol-cytotoxicity in eukaryotic cells may lead to the development of this redox-cycling agent as an alternative chemotherapeutic target.
    • Oxidative Stress Markers in Periodontitis: A Systematic Review

      Pacios Pujado, Sandra; Reidy, Mary Beth A. (2016)
      Purpose: The aim of the present systematic review was to analyze the role of oxidative stress markers in patients with periodontal disease. Materials and Methods: A comprehensive search based on predetermined inclusion criteria was performed to identify studies evaluating oxidative stress markers in humans with and without periodontitis. The search included all studies up to February 2016 in the following databases: Ovid MEDLINE, Scopus, and Cochrane Library. Results: The initial search identified 2,523 entries. The final selection consisted of 16 articles. The characteristics of the studies and the outcomes measures were described. Conclusions: A clear relationship is suggested for oxidative stress and periodontitis. Besides the outcome patterns demonstrated, the findings of the present systematic review underline the necessity of methodological standardization. Future research focusing on disease susceptibility, predictive, prognostic and therapeutics aims need to be explored.