Curcumin sensitizes human U-87 glioblastoma and MCF-7 breast cancer cells to the endocannabinoid reuptake inhibitor OMDM-2

Δ9-Tetrahydrocannabinol (THC), active constituent of Cannabis sativa L., possesses potential antitumor activity. Modulating endogenous levels of cannabinoids is a new strategy to avoid clinical and ethical considerations which limit the use of direct agonists. As dietary interventions may improve the effectiveness of cancer chemotherapy, we investigated the combinatory effect of the endocannabinoid reuptake inhibitor, OMDM-2, and the natural product curcumin, derived from Curcuma longa (L.), on cytotoxicity.

The in vitro antiproliferative activities of OMDM-2 alone or in combination with curcumin were evaluated against both, breast cancer (MCF-7) and glioma (U-87) cells, using resazurin assay. The effect of curcumin on OMDM-2 chemosensitivity was determined by comparing IC₅₀-values of OMDM-2 in absence and presence of curcumin. The additive, synergistic or antagonistic activity of the combination was evaluated by combination index (CI) and isobologram analyses.

OMDM-2 by itself showed antiproliferative effects against both MCF-7 and glioma with IC₅₀ of 4.9 and 2.7 µM, respectively. Co-exposure to curcumin increased the sensitivity of both cell lines to OMDM-2 in a dose dependent manner. The exposure to the ratio 1:8 of OMDM-2/curcumin decreased the IC₅₀ of curcumin to 1.8 in both cell lines. Isobole and CI analyses at different IC levels revealed that drug interaction was predominantly synergistic against MCF-7 cells. While in case of glioma cells, this combination could be synergistic or antagonistic depending on the ratio and concentration of drugs.

These findings provide experimental support for the use of curcumin as a modulator of tumor cell chemosensitivity in cannabinoid based therapies.