Abstract
Squamous cell carcinoma (SCC) is the second most common form of skin cancer in the world, presenting in nearly 1 in 5 US adults by age 70 alongside basal cell carcinoma. Localized low- and high-risk SCC is treated with surgical techniques offering favorable prognoses with recurrence being unlikely. Therapies for non-operable metastatic SCC, such as chemotherapy, possess undesirable side effects, and have yet to achieve similar response rates to surgery. Investigation into pharmacological targeting of cancer using cannabinoids is ongoing, demonstrating pre-clinical efficacy in various cancer models. Additionally, cannabinoids are established immunomodulatory compounds, capable of shifting immune cell populations, regulating immune cell trafficking, and their migration. Our study aimed to investigate the immunomodulatory, and anti-neoplastic capacity of REPYR-SC, a novel hemp extract. SCC-15 cells were used to model SCC, HEKa epidermal keratinocytes were used as a non-cancerous peripheral tissue model, and CTLL-2 T lymphocytes to screen for immune reactivity. REPYR-SC1 was dosed at 0 (control), 0.1, 0.5, 1, and 5 μL/mL and incubated with SCC-15 or HEKa cells for 36 and 72 hours, meanwhile 24 and 48 hours for CTLL-2 cells all at 37°C under 5% CO2 (initial cell density of 2.5 x 105 cells/mL). Cell counts were evaluated pre- and post-treatment with an automated cell counter, and cell viability was determined following treatment via trypan blue exclusion and morphological analysis. REPYR-SC1 induced a significant time- and dose-dependent reduction in proliferation and cell viability (p<0.001) in squamous cell carcinoma cell line SCC-15, as well as T lymphocytes. At a dose of 1 and 5 μL/mL at the 36- and 72-hour mark, 100% inhibition of proliferation was observed in SCC-15 cells and 25% at 5 μL/mL - 72 hours for HEKa cells. At a dose of 1 and 5 μL/mL at the 48-hour mark, 100% inhibition of proliferation was observed for CTLL-2 cells. These results support earlier evidence suggesting the immunomodulatory, and anti-neoplastic activity of cannabinoids. Further testing in-vivo is warranted, and the mechanism of action for REPYR-SC1 remains unknown. Nonetheless, cannabinoid-based compounds may still represent a novel chemotherapeutic modality with a favorable toxicity profile.