Authors
Grazia Romano, Valentina Morgera, Antonio Pezone, Samantha Messina, Paolo Rosa, Manuela Iovinella, Claudia Ciniglia, Maria Teresa Gentile, Antonio Porcellini, Antonia Feola
Published in
Molecular therapy. Oncology. Volume 34. Issue 3. Pages 201320. Sep 17, 2026. Epub Aug 12, 2026.
Abstract
Glioblastoma multiforme (GBM) is a lethal malignancy with limited therapeutic options. Its aggressive progression and resistance to standard therapy necessitate the development of novel therapeutic strategies. Plant-based compounds have emerged as promising candidates for therapeutic development modulating key targets in cancer. The Ruta graveolens displays anti-inflammatory, analgesic, and antimicrobial properties. Herein, we report the anticancer potential of R. graveolens water extract (RGWE) on long-term cultures of human glioblastoma and elucidate the regulatory mechanisms driving its effect. Secondary stabilized cell cultures (U-87 MG, T98MG, and U-138 MG) and primary cell culture (FCN, MZC, and GL18-15) were either treated with RGWE and/or cis-diamminedichloroplatinum (cisplatin, CDDP). Cytostatic responses were assessed by cell viability (TB exclusion test), cell cycle (propidium iodide [PI] staining), and apoptosis (Annex-V and caspase-3) assays. We demonstrate that RGWE slows U-87 MG growth without affecting apoptosis and arrests the cell cycle in the G2/M phase. Mechanistically, RGWE interferes with PKC/MEK/ERK signaling pathway, as assessed by western blot analysis, through PKC inhibition in its active form. Furthermore, the combination of RGWE and cisplatin enables the use of a sublethal dose of the latter (0.2 μg/mL), thereby reducing cytotoxicity and the resistance to the drug. These findings reveal a novel mechanism by which RGWE controls glioblastoma growth, highlighting the therapeutic potential of targeting the PKC/MEK/ERK axis in glioma treatment.
PMID:
42668569
Bibliographic data and abstract were imported from PubMed on 30 Aug 2026.
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