Discussion
Our results indicate that compounds from Cannabis sativa other than cannabinoids, like the flavonoid cannflavin A, can be cytotoxic to human bladder transitional carcinoma cells and that this compound can exert synergistic effects when combined with other agents. In vivo studies will be needed to confirm the activity of cannflavin A as a potential agent for bladder cancer treatment.
Methods
Two transitional cell carcinoma cell lines were used to assess the cytotoxic effects of the flavonoid cannflavin A up to 100 μM. We tested the potential synergistic cytotoxic effects of cannflavin A with gemcitabine (up to 100 nM), cisplatin (up to 100 μM), and cannabinoids (up to 10 μM). We also evaluated the activation of the apoptotic cascade using annexin V and whether cannflavin A has the ability to reduce invasion using a Matrigel assay.
Results
Cell viability of bladder cancer cell lines was affected in a concentration-dependent fashion in response to cannflavin A, and its combination with gemcitabine or cisplatin induced differential responses-from antagonistic to additive-and synergism was also observed in some instances, depending on the concentrations and drugs used. Cannflavin A also activated apoptosis via caspase 3 cleavage and was able to reduce invasion by 50%. Interestingly, cannflavin A displayed synergistic properties with other cannabinoids like Δ9-tetrahydrocannabinol, cannabidiol, cannabichromene, and cannabivarin in the bladder cancer cell lines.