The endocannabinoid system (ECS) provides regulatory functions in several cellular and physiological processes. It has also been found to play a role in control of cancer development. Our group found that breast cancer cells responded to cannabinoid receptor (CB) agonist treatments. This leads the activation of CB receptors in breast cancer, which inhibited their growth. In addition, breast cancer cells also behaved differentially when they were exposed to combinations of both CB1 and CB2 agonists. The underlying mechanism of individual- or co- activation after CB agonist exposure is still unknown. Hence, we studied the impact of CB activation on cancer molecular signature by performing proteomic analysis after triple-negative breast cancer (MDA-MB-231) cells exposed to CB receptor agonists. In this study, ACEA and GW405833 were used as CB1 and CB2 receptor agonists, respectively.