IADR Abstract Archives
Polygodial Analogs have Anti-Tumor Effects in Oral Squamous Cell Carcinoma that are Independent of TRPV1 Activity
Objectives: To assess the anti-tumor efficacy of Polygodial and novel analogs in vivo and determine if these effects involve TRPV1 activation.
Methods: Cell viability assays revealed candidate analogs for our in vivo studies. Mouse OSCC xenograft models were used to evaluate anti-tumor effects. Tumor-bearing mice were treated by intra-tumor injections every other day for two weeks with: 1) vehicle, 2) Polygodial, 3) analog P3, or 4) analog P10. Calcium imaging studies in CHO cells over-expressing TRPV1 and in OSCC cell lines were used to evaluate TRP channel activation in response to these compounds.
Results: Polygodial, P3, and P10 reduced OSCC viability in vitro. These results were reversible by the anti-oxidant N-acetyl-cysteine. Polygodial and P3 significantly reduced tumor growth by Day 12 and Day 14 respectively with Polygodial proving more efficacious. P10 was not effective in vivo. Calcium imaging revealed that P3 and P10 do not activate TRPV1 in vitro. However, Polygodial and P10 may activate other cation channels in OSCC cells.
Conclusions: Polygodial and P3 have significant anti-tumor activity in OSCC. P3 effects are independent of TRPV1 activation thus this novel therapeutic agent that may be used to treat OSCC without adverse side effects.
Methods: Cell viability assays revealed candidate analogs for our in vivo studies. Mouse OSCC xenograft models were used to evaluate anti-tumor effects. Tumor-bearing mice were treated by intra-tumor injections every other day for two weeks with: 1) vehicle, 2) Polygodial, 3) analog P3, or 4) analog P10. Calcium imaging studies in CHO cells over-expressing TRPV1 and in OSCC cell lines were used to evaluate TRP channel activation in response to these compounds.
Results: Polygodial, P3, and P10 reduced OSCC viability in vitro. These results were reversible by the anti-oxidant N-acetyl-cysteine. Polygodial and P3 significantly reduced tumor growth by Day 12 and Day 14 respectively with Polygodial proving more efficacious. P10 was not effective in vivo. Calcium imaging revealed that P3 and P10 do not activate TRPV1 in vitro. However, Polygodial and P10 may activate other cation channels in OSCC cells.
Conclusions: Polygodial and P3 have significant anti-tumor activity in OSCC. P3 effects are independent of TRPV1 activation thus this novel therapeutic agent that may be used to treat OSCC without adverse side effects.