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Flavonoids inhibit angiogenic cytokine production by human glioma cells
Sandra Freitas1, Silvia Costa, Camila Azevedo
1Laboratory of Neurochemistry, Health Sciences Institute, Federal University of Bahia, Brazil.
Abstract:
VEGF and TGF-β1 are cytokines that stimulate tissue invasion and angiogenesis. These factors are considered as molecular targets for the therapy of glioblastoma. Bevacizumab, a recombinant humanized monoclonal antibody developed against VEGF, inhibits endothelial cell proliferation and vessel formation. Flavonoids obtained from Dimorphandra mollis and Croton betulaster have been described as proliferation inhibitors of a human glioblastoma derived cell line. VEGF and TGF-β1 levels were dosed by ELISA in a GL-15 cell line treated with bevacizumab and also with the flavonoids rutin, 5-hydroxy-7,4'-dimethoxyflavone, casticin, apigenin and penduletin. Rutin reduced the VEGF and TGF-β1 levels after 24 h but not after 72 h. The other flavonoids significantly reduced TGF-β1 production. Bevacizumab reduced only the VEGF levels in the supernatant from GL-15 cultures. These results suggest that the flavonoids studied, and commonly used in popular medicine, present an interesting subject of study due to their potential effect as angiogenic factor inhibitors.
Insights
Flavonoids from Dimorphandra mollis and Croton betulaster show potential in inhibiting glioblastoma growth by reducing vascular endothelial growth factor (VEGF) and transforming growth factor-beta 1 (TGF-β1) levels.
Area of Science:
- Oncology
- Pharmacology
- Biochemistry
Background:
- Glioblastoma (GBM) is an aggressive brain tumor characterized by significant angiogenesis and invasion.
- Vascular Endothelial Growth Factor (VEGF) and Transforming Growth Factor-beta 1 (TGF-β1) are key cytokines driving GBM progression.
- Bevacizumab targets VEGF, while natural compounds are explored for novel therapeutic strategies.
Purpose of the Study:
- To investigate the inhibitory effects of specific flavonoids on VEGF and TGF-β1 production in a human glioblastoma cell line (GL-15).
- To compare the efficacy of these flavonoids with Bevacizumab in modulating angiogenic factors.
Main Methods:
- GL-15 cells were treated with Bevacizumab and various flavonoids (rutin, 5-hydroxy-7,4'-dimethoxyflavone, casticin, apigenin, penduletin).
- VEGF and TGF-β1 levels in cell culture supernatant were quantified using Enzyme-Linked Immunosorbent Assay (ELISA) at 24 and 72 hours.
- Statistical analysis was performed to determine significant differences in cytokine levels.
Main Results:
- Rutin demonstrated a reduction in both VEGF and TGF-β1 levels at 24 hours, but this effect diminished by 72 hours.
- Other tested flavonoids significantly decreased TGF-β1 production.
- Bevacizumab effectively reduced VEGF levels but did not impact TGF-β1 production.
Conclusions:
- The studied flavonoids exhibit potential as inhibitors of angiogenic factors relevant to glioblastoma.
- These natural compounds warrant further investigation for their therapeutic applications in cancer therapy.
- Flavonoids offer a promising avenue for developing novel anti-angiogenic strategies against glioblastoma.
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