Curcumin synergizes with the endocannabinoid reuptake inhibitor OMDM-2 in human MCF-7 breast cancer and U-87 glioblastoma cells

Introduction

Δ⁹-Tetrahydrocannabinol (THC), active constituent of Cannabis sativa L., possesses potential antitumor activity. Modulating the endogenous level of cannabinoids could be a sensible strategy to avoid adverse events presently limiting the use of direct agonists. We investigated the cytotoxicity of endocannabinoid reuptake inhibitor OMDM-2 alone and in combination with the polyphenol curcumin, an active compound of Curcuma longa L.

Methods

The in-vitro anti-proliferative activities of OMDM-2 alone/in combination with curcumin were evaluated in breast cancer (MCF-7) and glioblastoma (U-87) cells using the resazurin assay. The effect of curcumin on OMDM-2 was determined by comparing different inhibitory concentrations (IC) values of OMDM-2 in absence and presence of curcumin. The additive, synergistic or antagonistic activity of the combination was evaluated by the combination index (CI) and isobologram analyses.

Results

OMDM-2 by itself showed anti-proliferative effects against both MCF-7 and U-87 cells in a dose dependent manner with IC₅₀ values of 4.9 μM and 2.7 μM respectively. Isobol and CI analyses at different dose ratios revealed that the drug interaction was predominantly synergistic against MCF-7 cells (CI ≤ 0.5 at IC₅₀). While in case of glioblastoma cells CI values varied between <0.2 up to 1.1 at IC₇₀ depending on the ratio and concentration of the drugs.

Conclusion

These findings provide experimental support for the use of curcumin as a modulator of tumor cell pharmacointeraction in cannabinoid based therapies. To achieve synergism dose ratios should be established for each cell type and ratiometric dosing be considered.