South American Medicinal Plants as Sources of Antiglioblastoma Agents: a Systematic Review of In Vitro Evidence and Cell Death Mechanisms

Abstract Glioblastoma is the most common and aggressive primary malignant brain tumor in adults, and patient prognosis remains poor despite advances in standard therapeutic strategies. A major challenge in glioblastoma treatment is the tumor’s pronounced resistance to therapy, driven by extensive cellular heterogeneity, rapid adaptation, and activation of multiple survival pathways. These limitations have prompted growing interest in alternative and complementary approaches, including the investigation of plant-derived compounds with cytotoxic potential. Following the PRISMA 2020 guidelines, a systematic search of six academic databases was conducted up to August 2024 using predefined keywords. The initial search retrieved 1,122 records, of which 59 studies met the inclusion criteria after screening and eligibility assessment. This review focuses on in vitro studies evaluating the cytotoxic effects of South American medicinal plant extracts and isolated compounds on glioblastoma cell lines. The included studies demonstrated substantial methodological heterogeneity with respect to plant species and parts used, extraction methods, glioblastoma cell lines, treatment concentrations and exposure times, and outcome measures. Despite these differences, numerous plant-derived compounds exhibited antiglioblastoma activity, reducing cell viability and inducing cell death through multiple mechanisms, including apoptosis, autophagy, necrosis, and necroptosis. Overall, the findings highlight South American medicinal plants as a rich source of bioactive compounds with antiglioblastoma activity in preclinical models. While the evidence remains limited to in vitro systems, these results provide a rationale for further mechanistic studies, standardized experimental approaches, and in vivo investigations to assess bioavailability, safety, and therapeutic relevance, supporting the potential development of novel strategies for glioblastoma treatment. Graphical Abstract