Investigation of the anticancer effect of achillea biebersteinii afan in ependymal tumor culture cells

Although there are promising developments in cancer treatment, the treatment of ependymomas, a type of glioma with a very poor prognosis among brain cancers, is limited in terms of what is known. In this study, the anti-cancer effects of Achillea biebersteinii aqueous extract on the DKFZ-EPN1 cell line, which is a subtype of ependymomas, have been investigated. For this purpose, aqueous extract of Achillea biebersteinii was obtained by ultrasonic methods, the cytotoxic effects were determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) analysis, and groups were formed including control (no extract added), low (0,115 mg/mL), medium (IC50=0,241 mg/mL) and high (0,482 mg/mL). Apoptotic activity and cell cycle analyses were performed by flow cytometry method in all groups. The effect of the extract on Nuclear Factor Kappa B (NF-κB) and Transient Receptor Potential Canonical (TRPC)6 channel gene expression was determined by real-time PCR analysis. The effect of the extract on Transient Receptor Potential (TRP) channel currents was analyzed by patch clamp method, and the evaluation was made by measuring the maximum current value in the recordings. In addition, malondialdehyde levels and oxidative stress markers such as catalase, superoxide dismutase and glutathione peroxidase activities were analyzed. In cytotoxicity analyses, a decrease in cell viability compared to the control was detected in all groups (p<0,05). A decrease in gene expression values for both TRPC6 and NF-κB compared to the control was observed in all groups (p<0,01). A decrease in maximum current and conductance values compared to the control was determined in all groups in patch clamp analyses (p<0,05). In flow cytometry experiments, it was determined that the extract had a dose-dependent inhibitory effect on cell proliferation, induced apoptosis, and caused cell cycle arrest at the G1 phase. No significant changes were observed in the levels of catalase (CAT), glutathione peroxidase (GPx), superoxide dismutase (SOD) and malondialdehyde (MDA). As a result, it was observed that Achillea biebersteinii aqueous extract was dose-dependently cytotoxic to DKFZ-EP1NS cells, decreased TRPC6 and NF-kB gene expressions, blocked TRP channel currents, depending on these results inhibited cell proliferation and induced apoptosis. Although these results suggest that Achillea biebersteinii aqueous extract can be used as a curative phytotherapeutic agent for ependymoma, more comprehensive studies including in vivo and clinical studies are needed.