Abstract B019: Investigating Cannabis sativa bioactive compounds as an anti-cancer treatment in high-grade serous ovarian cancer

Introduction High-grade serous ovarian cancer (HGSOC) is the most common and aggressive form of epithelial ovarian cancer. Although most patients respond to first-line treatment with chemotherapy, resistance ensues in 80 – 90% of patients with metastatic disease. Therefore, there is an unmet need to develop novel therapeutics. Cannabis sativa bioactive compounds, cannabidiol (CBD) and cannabigerol (CBG), have been shown to exert anti-cancer effects in in vitro cancer models. Cannabinoids reduce cell tumor viability, invasion and migration and induce apoptosis. Cannabinoid medicines, including nabilone and dronabinol, are FDA-approved for the treatment of nausea and vomiting associated with chemotherapy. Therefore, there is potential in cannabinoid medicine to offer a dual effect of anti-cancer activity along with negating side effects of treatment. The aim of this research is to investigate Cannabis sativa bioactive compounds for the treatment of HGSOC. Experimental Procedures: HGSOC cell lines (COV318, OVCAR-4 and CAOV-3) and a non-cancerous fibroblast cell line (HFF2) were treated with CBD, CBG and cannabidiolic acid (CBDA) (0 µM – 100 µM) for 24, 48, 72 and 144 hours, and carboplatin (0 µM – 1,024 µM) and paclitaxel (0 - 10 µM) for 72 hours to establish their effects on cell viability and establish IC50 values, using the MTT assay. This data informed the design of combination experiments to investigate synergy between cannabinoids and chemotherapy. To establish the effect of cannabinoids on cell migration, cell lines (COV318 and OVCAR-4) were treated with a non-toxic dose of CBD and CBG and subjected to a wound healing assay. Results: CBD, CBG and CBDA significantly reduced the viability of the COV318, OVCAR-4 and CAOV-3 cell lines in a dose-dependent manner. CBD is the most efficacious cannabinoid resulting in the greatest reduction in viability of the HGSOC cell lines, with an IC50 value of 11.82 µM (CAOV-3), 20.09 µM (OVCAR-4) and 25.59 µM (COV318) after 72 hours. CBDA had no effect on viability of COV318 and OVCAR-4 cell lines at 72 hours, however at 144 hours, CBDA significantly reduced the viability of the OVCAR-4 cell line with an IC50 value of 34.25 µM. Interestingly, CBDA had no effect on viability of the HFF2 cell line at 144 hours, whereas CBD and CBG reduced HFF2 viability, suggesting a cancer selective effect of CBDA. Treatment with carboplatin and paclitaxel significantly reduced viability of COV318, OVCAR-4 and CAOV-3 cell lines in a dose-dependent manner. CBD significantly reduced the migratory capacity of COV318 and OVCAR-4 cell lines by 15.4% at 36 hours and 12.61% at 54 hours, respectively. Conclusion: Cannabinoids, CBD, CBG and CBDA represent a viable and exciting opportunity to develop novel therapeutics for HGSOC. Ongoing research is investigating the effect of these cannabinoids on other cancer hallmarks (invasion and apoptosis) and investigating synergy between cannabinoids and chemotherapy in HGSOC.

Citation Format: Claire Hughes, Rianna Magee, William Gallagher, Susanne Schilling, Antoinette Perry. Investigating Cannabis sativa bioactive compounds as an anti-cancer treatment in high-grade serous ovarian cancer [abstract]. In: Proceedings of the AACR Special Conference on Ovarian Cancer; 2023 Oct 5-7; Boston, Massachusetts. Philadelphia (PA): AACR; Cancer Res 2024;84(5 Suppl_2):Abstract nr B019.