Anticancer Potential of Artemisia annua L. Extracts Against Glioblastoma: Apoptosis and Necroptosis Pathway Modulation

Abstract

Introduction Glioblastoma is a highly aggressive and treatment-resistant brain tumor with poor prognosis. Conventional therapies, including surgery, chemotherapy, and radiotherapy, provide limited efficacy due to tumor resistance. Natural compounds from Artemisia annua L. have shown promise as alternative treatments, particularly polyphenols like chlorogenic acid, which may induce apoptosis and necroptosis in cancer cells (1-3). Aim To investigate the anticancer effects of Artemisia annua L. extracts on glioblastoma cells, focusing on polyphenolic compounds and their interaction with apoptosis- and necroptosisrelated proteins. Methods High-performance liquid chromatography quantified the main polyphenols using UV absorption at a wavelength range of 300–400 nm. 10 μL of A. annua L. extract was used for the HPLC analysis. Molecular docking studies were carried out using AutoDock Vina 4.05. All docking parameters were left at default values. The box space covered all the interior of the protein studied and the protein itself. Structures with the lowest docking energy, that is, the highest affinity to the studied protein, were analyzed using PyMOL. Cytotoxicity assays assessed the viability of C6 glioma cells following A. annua L. extract treatment. Results Chlorogenic acid was the most abundant polyphenol, followed by luteolin and isoquercitrin. Docking studies showed strong binding between chlorogenic acid and MLKL/RIPK3, suggesting involvement in necroptosis. A. annua L. extracts significantly reduced glioblastoma cell viability, with concentrations above 50 µg/ml inducing necrotic cell death. The whole extract exhibited greater cytotoxicity than chlorogenic acid alone, indicating synergistic effects. Conclusions Artemisia annua L. extracts demonstrate potent anticancer activity in glioblastoma cells by inducing apoptosis and necroptosis. These findings highlight A. annua L. as a potential glioblastoma treatment, warranting further research.