Cannabinoids and standardized cannabis extracts inhibit migration, invasion, and induce apoptosis in MCF-7 cells through FAK/MAPK/Akt/NF-κB signaling.

BACKGROUND: Breast cancer is the highest incidence of all types of cancer in women, and the cancer metastasis process accounts for a majority of cancer deaths. Two major cannabinoids, Δ-9-tetrahydrocannabinol (THC) and cannabidiol (CBD), from Cannabis sativa are expected to have anti-cancer activity. This study aimed to investigate the effects of THC, CBD, and standardized cannabis extracts (F1, F2, and F3) on migration, invasion, and apoptosis of human breast cancer (MCF-7) cells. METHODS: Cell viability, survival, and apoptosis were determined using the MTT, clonogenic, and nuclear staining assays, respectively, while cancer cell migration and invasion were evaluated by the wound healing, trans-well, and filopodia assays. Western blot analysis was used to find out the mechanisms of the cannabinoids against MCF-7 cells. RESULTS: CBD, THC, and F1 inhibited filopodia formation, migration, and invasion of MCF-7 cells through suppressing the expression of the FAK, Akt, ERK1/2, p38MAPKs, and NF-κB upstream pathways, as well as inhibiting the Rac1/Cdc42 downstream pathways. In addition, CBD significantly inhibited the mTOR pathway. Furthermore, CBD and F1 induced apoptosis in MCF-7 cells via the Bcl-2/caspase-3 pathways. CONCLUSION: These results indicate that THC, CBD, and F1 have great abilities for preventing breast cancer cell metastasis in in vitro experiments.

α-Glucosidase inhibitory activity of cannabidiol, tetrahydrocannabinol and standardized cannabinoid extracts from Cannabis sativa.

Two major cannabinoids of cannabis, namely cannabidiol (CBD) and tetrahydrocannabinol (THC) have been reportedly used as alternative medicine for diabetes treatment in both pre-clinical and clinical research. However, their mechanisms of action still remain unclear. Therefore, this study aimed to evaluate the α-glucosidase inhibitory activity of THC, CBD and the standardized cannabinoid extracts. Based on in silico studies, THC generated hydrogen bonding and Van der Waals interactions, while CBD exhibited only Van der Waals interactions with functional residues of target α-glucosidase protein, with good binding energies of -7.5 and -6.9 kcal/mol, respectively. In addition, both of them showed excellent pharmacokinetic profiles with minor toxicity in terms of tumorigenic and reproductive effects. In addition, the enzyme based in vitro assay on α-glucosidase revealed that THC and CBD exhibited good inhibitory activity, with the IC50 values of 3.0 ± 0.37 and 5.5 ± 0.28 µg/ml, respectively. These were better than the standard drug, acarbose (IC50 of 488.6 ± 10.23 µg/ml). Furthermore, two standardized cannabinoid extracts, SCE-I (C. sativa leaf extract) and SCE-II (C. sativa inflorescence extract) exhibited stronger inhibitory activity than THC and CBD, with the IC50 values of 1.2 ± 0.62 and 0.16 ± 0.01 µg/ml, respectively. The present study provides the first evidence that the standardized cannabinoid extracts containing THC and CBD have greater potential than CBD and THC in application as an α-glucosidase inhibitor.