Cancer cells possess heightened rates of cell proliferation due to aberrant cellcycle checkpoints. Cannabidiol (CBD) has been shown to down... Show moreCancer cells possess heightened rates of cell proliferation due to aberrant cellcycle checkpoints. Cannabidiol (CBD) has been shown to down-regulate expression of the inhibitor of DNA-1 (Id-1), a basic helix-loop-helix transcription regulator that controls breast cancer metastasis. CBD is a cannabinoid that does not act efficiently with the known cannabinoid (CB1 and CB2 ) receptors. We studied the link between the ability of CBD to stimulate reactive oxygen species (ROS) production and its ability to inhibit cell viability. The CB1/CB2 receptor partial agonist Δ⁹- Tetrahydrocannabinol could not produce significant amounts of ROS except at a very high concentration demonstrating the unique ability of CBD to generate ROS is not due to CB1 and CB2 activation. Using multiple breast cancer cell lines, we determined the effects of CBD on ROS production were a concentration-dependent and occurred across a majority of breast cancer cell lines evaluated (human and mouse). We also analyzed whether the CB2-receptor selective antagonist SR144528 (SR2) and an ROS scavenger, α-tocopherol (TOC or vitamin E) could reverse the effects of CBD. The CB2 receptor antagonist could only partially reverse the inhibition of cell viability and stimulation of ROS production produced by CBD. TOC however could completely reverse the effects of CBD. To determine whether CBD stimulation of ROS was an effect specifically produced in breast cancer cell lines, we studied this effect in non-transformed human fibroblast cells. CBD produced negligible amount of ROS in non-transformed cells and xii was significantly less effective at inhibiting the viability of the fibroblast, suggesting that CBD must be acting through mechanisms unique to transformed cells. Here, we report that CBD inhibits breast cancer cell viability through efficient stimulation of ROS which is possibly mediated through unique interaction with the cannabinoid system, other than the mechanism of CB1 and CB2 receptor activation. M.S. in Biology, December 2012 Show less
