Anticarcinogenic Properties of Malic Acid on Glioblastoma Cell Line Through Necrotic Cell Death Mechanism

Abstract

This study aimed to investigate the anticarcinogenic and genotoxic damage potentials of malic acid on human fibroblast cells (HDFa) and glioblastoma (U87-MG) cell lines. MTT cell viability and LDH release assays were performed to understand cytotoxic features of malic acid on different cell lines. Also, Hoechst 33258 fluorescent staining was used to monitor nuclear abnormalities including micronucleus, lobbed, and notched structures. Furthermore, cellular death mechanisms behind the malic acid application were investigated via the use of flow cytometry analysis. According to cell viability analysis, malic acid showed a greater effect on U87-MG compared to HDFa cell line in terms of cytotoxicity. Similarly, chromosomal integrity assay put forth a higher number of nuclear abnormalities in U87-MG cells when compared to HDFa cell lines, and aberrations were analyzed to amplify when malic acid concentration increased. Finally, flow cytometry analysis demonstrated higher necrotic cell death in U87-MG cells than HDFa cell line. On the other hand, apoptotic cell death was the main cytotoxic mechanism against malic acid exposure in the HDFa cell line. In light of these results, it can be concluded that in higher concentrations, malic acid has an anticarcinogenic effect on glioblastoma cells via the necrotic pathway, and it also shows apoptotic properties on the fibroblast cell line. When mutagenic properties are compared, it could be understood that malic acid had a greater impact on glioblastoma cells.