Abstract
4-thiazolidinones, which are privileged structures in medicinal chemistry, comprise the well-known class of heterocycles and are a source of new drug-like compounds. Undoubtedly, the 5-bulky-substituted-2,4-thiazolidinediones - a class of antihyperglycemic glitazones, which are peroxisome proliferator-activated receptor gamma (PPARγ) agonists, are the most described group among them. As there are various chemically distinct 4-thiazolidinones, different subtypes have been selected for studies; however, their main pharmacological profiles are similar. The aim of this study was to evaluate the anticancer activity of 5Z-(4-fluorobenzylidene)-2-(4-hydroxyphenylamino)-thiazol-4-one (Les-236) in four human cancer cell lines, A549, SCC-15, SH-SY5Y, and CACO-2, and investigate its impact on the production of reactive oxygen species (ROS) and the apoptotic process as well as cytotoxicity and metabolism in these cell lines. The cell lines were exposed to increasing concentrations (1 nM to 100 µM) of the studied compound for 6, 24, and 48 h, and later, ROS production, cell viability, caspase-3 activity, and cell metabolism were examined. The obtained results showed that the studied compound decreased the production of ROS, increased the release of lactate dehydrogenase, and decreased cell metabolism/proliferation in all the five cell lines at micromolar concentrations. Interestingly, over a wide range of concentrations (from 1 nM to 100 µM), Les-236 was able to increase the activity of caspase-3 in BJ (after 6 h of exposure), A549, CACO-2, and SCC-15 (after 48 h of exposure) cell lines which could be an effect of the activation of PPARγ-dependent pathways.
Highlights
Among the 5-ene-2-amino(imino)-4-thiazolidinones, active anticancer agents which are capable of inhibiting the growth of cancer cells were identified both in screening campaigns and small-scale studies[15,16,17,18,19,20,21]
Our experiments showed a decrease in reactive oxygen species (ROS) production in all the studied cancer cell lines (SCC-15, CACO-2, A549, and SH-SY5Y) and the normal skin fibroblast cell line (BJ) under the action of Les-236
The strongest decrease in ROS production in all the time intervals was observed in CACO-2 cell line, while SH-SY5Y cell lines showed the least sensitivity to Les-236
Summary
Among the 5-ene-2-amino(imino)-4-thiazolidinones, active anticancer agents which are capable of inhibiting the growth of cancer cells were identified both in screening campaigns and small-scale studies[15,16,17,18,19,20,21]. Analyses of the molecular mechanisms of their action revealed their role in the following processes: induction of apoptosis, cell cycle arrest[31,32,33], PPAR-related pathways[20,25], inhibition of necroptosis[34,35], and modulation of Red/Ox signaling and production of reactive oxygen species (ROS). Analyses of the effects of 5-ene-2-amino(imino)-4-thiazolidinones revealed the importance of these metabolic pathways in anticancer activity[1,2]. The aim of this study was to evaluate the anticancer activity of 5Z-(4-fluorobenzylidene)-2-(4-hydroxyphenylamino)-thiazol4-one (Les-236) in four human cancer cell lines A549, SCC-15, SH-SY5Y, and CACO-2, and investigate its impact on ROS production and the apoptotic process as well as cytotoxicity and metabolism in these cell lines (Fig. 1)
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
