Background: A glioblastoma is a primary CNS tumor that is more aggressive and lethal than other
brain tumors. Its location, rapid proliferation, invasive growth, angiogenesis and immunosuppression are the
main factors that limit its treatment, making it a major challenge to neuro-oncology.
Objective: This study investigated the in vitro effects of the alkaloid dihydrochelerythrine (DHC), which is
extracted from Zanthoxylum stelligerum, on the viability, proliferation, cell death and β-catenin, NFκB,
STAT3/pSTAT3 and interleukins roles.
Method: In vitro experimental models of human (U251 and GL-15) and murine (C6) glioblastoma cells were
cultured in the presence of DHC at increasing concentrations for MTT assay and exclusion trypan blue dye to
determine EC50. Afterward, C6 and U251 cells were treated with 100 µM DHC or DMSO 0.1% for cell cycle,
annexin and expression of β-catenin/NFκB/STAT3/pSTAT3 by flow cytometry or immunofluorescence. Interleukin
quantification was made by Cytometric Bead Array.
Results: A significant decrease was observed in C6 and U251 cell viability in a time and dose-dependent manner.
GL-15 cell viability decreased only when treated with 200 µM DHC. This maximum concentration affected
neither astrocytes nor microglia viability. A cytostatic effect of DHC was observed in C6 and U251 cells after
48 h of 100 µM DHC treatment. After 72 h of DHC treatment, C6 presented 80% of annexin-V+ cells compared
to 10% of annexin-V+ U251 cells. C6 cells demonstrated significant high levels of NFκ B and β-catenin cytoplasmic
fraction. Additionally, DHC treatment resulted in higher significant levels of IL-6 than did other interleukins
and STAT3 up-regulation in U251 cells.
Conclusion: These results demonstrate that DHC acts as a chemosensitizing agent selective for glioma cells not
affecting non-tumor cells. Considering tumor heterogeneity, DHC demonstrated an anti-cancer potential to
activate different cell death pathways. DHC demonstrated could be used for chemotherapy and immunotherapy
applications in glioblastomas in the future.