PLANT-BASED ADJUVANT STRATEGIES TARGETING TUMOR CELLS: FUNCTIONAL CHARACTERIZATION OF THE RZERO EXTRACT

Glioblastoma multiforme (GBM) is a high-grade astrocytic tumor arising from glial cells, characterized by its invasive and infiltrating nature. Natural plant extracts offer promising therapeutic potential due to their rich repertoire of bioactive compounds—such as polyphenols, flavonoids, and terpenoids— shown to modulate numerous signaling pathways both in physiological and pathological conditions. Searching for novel approaches to GBM and glioblastoma stem-like cells (GSCs), our research group became interested in the plant-based compound RZERO.
In our study, we characterized the polyphenol and flavonoids concentrations, and antioxidant power of this complex extract. Preliminary in vitro data, demonstrate its cytotoxic effects on T98 human GBM and CT2A mouse GBM lines alongside alterations in cancer stem cell markers expression. Furthermore, we observed an enhancement of immune cell activation and cytokine profiles against tumor cells. These findings pave the way for additional preclinical evaluation. Ongoing in vivo studies in both Drosophila melanogaster and Severe Combined Immunodeficiency mice (SCID), which lack functional T and B lymphocytes, administered with previously selected doses of RZERO, further corroborate our in vitro findings, demonstrating a significantly reduced tumor growth in vivo.
Current efforts focus on identifying the specific bioactive components in RZERO responsible for its cytotoxicity and immunomodulatory effects using HPLC-MS analysis. In parallel, we are investigating its possible synergy with temozolamide chemotherapy by determining the IC50 thought growth rate assays. To elucidate the underlying mechanisms, we analyze alterations in protein expression and cytokines secretion profiles in co-cultured GBM and immune cells.