Albanol B inhibits glioblastoma progression by inducing senescence and apoptosis via the RNF6/p27 signaling axis.

Background: Glioblastoma, the most devastating type of glioma, is notorious for rapid proliferation, aggressive infiltration, angiogenesis, and treatment resistance. Identifying effective medicines or adjuvants for clinical therapy is imperative. Albanol B (ABN-B), a prenylated arylbenzofuran isolated from the mulberry tree, demonstrates neuroprotective, anti-inflammatory, and anti-cancer properties. However, the biological effect of ABN-B in glioblastoma remains unclear.

Purpose: To investigate the anti-tumor effects of ABN-B on glioblastoma progression and elucidate its molecular mechanisms.

Methods: MTT assays, EdU staining, γ-H2AX immunofluorescence, SA-β-galactosidase staining, TUNEL staining, and colony formation assays were performed to assess the suppressive action of ABN-B on glioblastoma cells in vitro. Mechanistic insights were obtained through Western blotting, RT-qPCR, and AutoDock-based molecular docking. In vivo efficacy was evaluated using a xenograft mouse model.

Results: ABN-B dose-dependently repressed cell growth while inducing senescence and apoptosis. Mechanistically, the oncogenic protein RNF6 interacts with p27 and directly ubiquitinates it via E3 ligase activity, and it also indirectly accelerates p27 ubiquitination and degradation by activating SKP2 transcription. ABN-B promoted ubiquitin-mediated degradation of RNF6, reducing RNF6 protein stability. This further targeted the RNF6/p27 signaling pathway and inhibited glioblastoma progression.

Conclusion: ABN-B inhibits glioblastoma by inducing cell cycle arrest, senescence, and apoptosis through destabilizing RNF6 and disrupting the RNF6/p27 pathway. Our findings reveal the anti-cancer effect of ABN-B and suggests its potential as a therapeutic candidate or adjuvant for glioblastoma therapy.