In Vitro Cytotoxicity of Cyanuric Acid and Selected Derivatives

Abstract

Background
Cyanuric acid and its derivatives belong to the group of s-triazines. They have wide industrial application, generally in the production of pesticides, bleaching agents and disinfectants. Recent reports showed significant negative effect of cyanuric acid in combination with melamine but low general cytotoxicity of cyanuric acid alone. However, evaluations of cyanuric acid toxicity against different human cell types using a panel of in vitro assays have not been performed. In addition, little is known about the cytotoxicity and potential antitumor effects of certain cyanuric acid derivatives, for example trichloroisocyanuric acid and 1,3,5-tris(2-hydroxyethyl) isocyanurate.
Aim
To investigate the toxicity of cyanuric acid, trichloroisocyanuric acid and 1,3,5-tris(2-hydroxyethyl) isocyanurate using different cancer cell lines and normal fibroblasts.
Materials and Methods
MTT, Neutral red and clonogenic assays were used to characterize the in vitro cytotoxicity of cyanuric acid, trichloroisocyanuric acid and 1,3,5-tris(2-hydroxyethyl) isocyanurate. Different concentrations of the compounds were tested on three cancer cell lines (HeLa, A549, CaOV) and normal human fibroblasts. IC50 values were calculated and compared. Intracellular ATP measurements and microscopic evaluations of cellular morphology after exposure to cyanuric acid, trichloroisocyanuric acid and 1,3,5-tris(2-hydroxyethyl) isocyanurate were performed.
Results
Among the three test-agents trichloroisocyanuric acid (TCIC) demonstrated the highest cytotoxicity in vitro. Interestingly, MTT assays indicated that the toxic effects of TCIC were mainly directed towards cancer cells affecting mitochondrial functionality. Clonogenicity of cancer cell lines was completely inhibited in the presence of low concentrations of the triazine. Exposition to TCIC influenced the morphology and intracellular ATP concentration in both cancer cells and normal fibroblasts but the observed effects were stronger in cancer cells.
Conclusion
The order of cytotoxicity of the tested compounds is as follows: trichloroisocyanuric acid>cyanuric acid>1,3,5-tris(2-hydroxyethyl) isocyanurate. Trichloroisocyanuric acid demonstrates selective antitumor effect.