Abstract C112: Hemp extract attenuates the proliferation of hepatocellular carcinoma cells- derive cells from racially diverse populations by inhibiting the Interferone-1 signaling pathway

Abstract Hepatocellular Carcinoma (HCC) is a highly fatal disease where race/ethnicity plays a vital role in determining incidence, mortality, and survival rates. The incidence of HCC is highest in Asia and Africa. Furthermore, there is a statistically significant increase in incidence and mortality and a decrease in 5-year survival rates in African American (AA)/Black patients compared to non-Hispanic white patients. The HCC patients might benefit from a holistic dietary approach, including hemp extract, along with their clinical treatment. Our bioinformatics analysis of The Cancer Genome Atlas (TCGA) identified the IFN-I signaling genes (ISGs) as the most significantly enriched pathway in AA/Black HCC patients. Consistent with this finding, RNA-seq analysis of archived HCC tumors from white (n=14) and AA/Black (n=18) patients further confirmed the upregulation of ISGs in these cohorts. Due to the severe toxicity of the currently available cancer treatments, there is also a demand for the development of alternative therapies with high efficacy and low side effects. We characterized 16 varieties of hemp for their polyphenols, antioxidation, CBDs, and terpenes contents and determined the effects of hemp extracts on the proliferation of HepG2 (white patients), Hep3B, and O/20 (Black patients), and HuH-7 (Asian Patient) HCC cell lines. Among different hemp varieties, KY-Plume extract showed the highest concentration of polyphenols, antioxidation activity, CBDA, and terpenes. It also most potently inhibited the growth of all HCC cell lines (IC50s 20-25 mg/ml), irrespective of their racial origin. Hemp treatment reduced the phosphorylation of the IFN downstream mediators, Jak-1, Tyk2, STAT1, and STAT2, in all HCC cell lines. In addition, hemp treatment also inhibited phosphorylation/activation of PI3K-Akt-mTOR and MAPK pathways. Currently, research is underway to identify the active chemical agent in hemp and test it on other patient-derived HCC lines and in an in vivo model. In conclusion, our data suggest that hemp can attenuate HCC proliferation by inhibiting multiple cellular signaling pathways, including the IFN-1 pathway. Our data suggest that HCC patients might benefit from a holistic dietary approach, including hemp extract, along with their clinical treatment. (Funded: Even-Allen-USDA and P20 CA264068-01-NIH). Citation Format: Rafat A Siddiqui, Haiwen Li, Ramesh Dhakal, Milton O Faison, Devanand Sarkar.. Hemp extract attenuates the proliferation of hepatocellular carcinoma cells- derive cells from racially diverse populations by inhibiting the Interferone-1 signaling pathway [abstract]. In: Proceedings of the 17th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2024 Sep 21-24; Los Angeles, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2024;33(9 Suppl):Abstract nr C112.