Abstract:
Cannabis sativa L. (C. sativa) is a medicinal plant that has been used for at least 1800 years according to ancient writings. Extensive studies were conducted to determine the full extent of its therapeutic potential. Among several compounds detected, the Δ9-tetrahydocannabinol (THC) and the cannabidiol (CBD) are the most thoroughly investigated compounds. In this study we aim to investigate the anticancer activity of cannabinoids mixture isolated from the Lebanese C. sativa plant. A mixture of CBD and THC in ratios comparable to the local medicinal plant was used in this study to elucidate its mechanism of action in breast cancer cells, MDA-MB-231 and MCF-7, in vitro. Breast cancer cell lines treated with increasing CBD/THC mixture concentrations were subjected to cytotoxicity assay, cell cycle analysis, Annexin V/ PI dual staining, cell death ELISA, western blot analysis of apoptotic and autophagy markers. We further evaluated the effect of the cannabinoids on inhibiting the motility of MDA-MB-231 using the wound-healing and transwell migration assays. Our results revealed the promising therapeutic benefits of CBD/THC mixture on inhibiting the growth of breast cancer cells by promoting cellular fragmentation, phosphatidylserine translocation to the outer membrane leaflet and DNA fragmentation in both cell lines while inhibiting the motility of the triple negative breast cancer cells. In our study, CBD/THC mixture was found to exhibit a pro-apoptotic activity via the activation of the mitochondrial apoptotic pathway, independent from ROS production while also suggesting the activation of a caspase-dependent apoptotic pathway. Even though autophagy is up regulated upon exposure to cannabinoid mixture, it is not the main cause inducing cell death. In conclusion, our study demonstrates the promising therapeutic benefits of CBD and THC isolated from the Lebanese C. sativa plant on breast cancer cells in vitro.
