Preclinical Study of Cannflavins A and B Action Against Glioblastoma Cells

Background

Flavonoids represent a large group of naturally occurring polyphenolic compounds, many of which have been found to produce valuable biological outcomes, including action against cancer cells. Glioblastoma multiforme (GBM) is an aggressive type of brain tumor that is associated with a poor prognosis and has limited treatment options. Previous findings suggest that cannflavins can produce promising effects for pancreatic and bladder cancers, but the efficacy of these phytochemicals in attacking brain tumour cells remains unknown. Our study evaluates the potential of cannflavin A and cannflavin B against GBM cells using a range of in vitro approaches.

Results

We conducted experiments using A-172 and U-87 GBM lines to assess the impact of cannflavins A and B on cell viability, cycle, migration, and invasion capacity. Our results revealed a consistent dose-dependent decrease in cell viability in both lines after the addition of cannflavin B to the culture media. Interestingly, we found that chrysoeriol (the non-prenylated synthesis precursor of cannflavins in the Cannabis sativa plant) only has a limited adverse effect on survival using the same approach, while techtochrysin (an O-methylated flavone) has none. Using time-lapse live-cell imaging and a scratch assay, we also show that cannflavins can inhibit tumor cell migration at concentrations below those that produce significant cell death. Finally, we found that cannflavin B exhibits anti-migratory and anti-invasive properties in transwell and tumorsphere assays, underscoring its multifaceted therapeutic potential.

Conclusion

These findings suggest that cannflavin B holds promise as a therapeutic agent in the treatment of GBM.

H ighlights

• Cannflavin B but not cannflavin A limits the viability of A-172 and U-87 GBM cells in a concentration- and time-dependent manner.

• Using time-lapse live-cell imaging and a scratch assay, we provide evidence that cannflavins A and B can inhibit GBM cell migration at concentrations below those that result in a significant reduction in cell viability.

• Cannflavin B exhibits robust anti-migratory and anti-invasive properties in transwell and tumorsphere assays, underscoring its multifaceted therapeutic potential.

• Although previous work had reported the capacity of cannflavins A and B to interfere with TrkB and downstream the MAPK/AKT signaling pathways in mouse primary neurons, the effect of those molecules is limited in GBMs, suggesting that other targets are engaged to produce the cellular effects.