CBD as therapeutic agent for malignant glioma

Richter, Sven (2026): CBD as therapeutic agent for malignant glioma. Dissertation, LMU München: Faculty of Medicine

Abstract

Glioblastoma is a highly aggressive and malignant tumor with an inauspicious prognosis. Its rapid proliferation and invasive properties can, at least in part, be attributed to the transcription factor NF-κB. The cannabinoid cannabidiol has been shown to exert a cytotoxic effect in certain cannabidiol-sensitive glioblastoma cells. Interestingly, while cannabidiol promotes the nuclear accumulation of NF-κB, it simultaneously inhibits its phosphorylation at serine 311, which is an essential modification for its function as a transcription factor. In the first part of this publication, the relevance of NF-κB translocation was examined in more detail. Cytotoxicity assays demonstrated that co-application of the NF-κB sn50 inhibitor completely abolished the cytotoxic effect of cannabidiol, indicating that NF-κB translocation is essential for mediating the cytotoxic response to cannabidiol. Supporting this, immunocytochemical staining revealed that the inhibitor effectively prevented NF-κB from translocating into the nucleus in the same cells. These findings suggest that translocation and consecutive nuclear accumulation of NF-κB lacking phosphorylation at serine 311 is critical for the cytotoxic effect of cannabidiol in cannabidiol-sensitive glioblastoma cells. The second part of this publication further investigated the role of protein kinase C zeta in glioblastoma cells, given its ability to phosphorylate NF-κB at serine 311, a modification critical for transcriptional activity related to cell survival. Viability assays demonstrated that PKCζ is present in glioblastoma cells, as evidenced by a reduction in cell numbers following the application of a PKCζ pseudosubstrate. This observation was further confirmed by immunocytochemical staining. However, CBD application led to varying effects on PKCζ expression across the investigated cell lines, with some showing increased expression, others unchanged levels, and some a reduction.

• Item Type: Theses (Dissertation, LMU Munich)
• Keywords: GBM, CBD, NF-κB, NFkB, PKCZ
• Subjects: 600 Technology, Medicine; 600 Technology, Medicine > 610 Medical sciences and medicine
• Faculties: Faculty of Medicine
• Language: English
• Date of oral examination: 12. February 2026
• 1. Referee: Glaß, Rainer
• Signature of the printed copy: 0700/UMD 22724