Ortho-coumaric acid derivatives with therapeutic potential in a three-dimensional culture of the immortalised U-138 MG glioblastoma multiforme cell line
Y.K. Gutiérrez Mercado, J.C. Mateos Díaz, Doddy Denise Ojeda-Hernández, F.J. Gonzalez, Edwin E. Reza-Zaldívar, Mercedes A. Hernández-Sapiéns, Ulises A. Gómez Pinedo, Rosendo Estrada, Monserrat Macías-Carballo, Amable Aguirre
Abstract
Introduction The treatment of such primary brain tumours such as glioblastoma multiforme (GBM) presents numerous difficulties, considerably impacting patient survival rates . The search for new compounds with therapeutic potential focuses on the identification of molecules that can be produced through chemical and enzymatic processes and that present anticancer effects in different types of tumours. Methods Given the need for new treatments for GBM, we conducted a study to synthesise ortho-coumaric acid alkyl esters (OCAAE) and to evaluate them in an appropriate study model, a three-dimensional (3D) culture using the Matrigel extracellular matrix. We tested cytotoxicity with the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) technique and by determining phosphatidylserine externalisation with annexin V and active caspase-3 expression as markers of apoptosis, and the subsequent degradation of DNA as a marker of cell death. Results Medium-chain OCAAEs, such as butyl-o-coumarate (BOC) and its isomer, showed the greatest effect on most of the parameters evaluated in 3D cultures of GBM, followed by methyl-, propyl-, and ethyl-o-coumarate (MOC, POC and EOC); these compounds showed effects both in reducing cell viability and in increasing the expression of active caspase-3 and annexin V and the degradation of DNA, in comparison with the first-line treatment for GBM, temozolomide . Conclusion These results, together with those of previous researchers, show that the different OCAAEs have a potential therapeutic effect on GBM, and that 3D culture of GBM cells is an appropriate model for the study of new antitumour molecules.