LAUSR

Recently, the incidence of colorectal cancer (CRC) has been increasing year by year and has become the first incidence cancer in Taiwan. Epidermal growth factor receptor inhibitor (EGFR inhibitor) has been recognized as an important target of CRC. Therefore, targeting EGFR and its related signaling could be a potential strategy to overcome this disease. Hyperforin is a natural prenylated phloroglucinol and has been identified as the major molecule responsible for the antidepressant effects. Previous studies indicated that hyperforin has other potentially pharmacologically meaningful biological properties, including antibacterial ability and inhibition of inflammatory mediators. Numerous studies have also pointed out the anti-tumor potential of hyperforin is associated with the induction of apoptosis signaling. However, whether hyperforin may regulate CRC progression and its underlying mechanism is unclear. In our study, we used the MTT assay to prove the cytotoxicity of CRC cells (HT29 and HCT116 cells) was induced by hyperforin. We then used the flow cytometry to confirmed that hyperforin may induce both extrinsic/intrinsic apoptotic pathways in CRC cells. We further demonstrated hyperforin-induced apoptosis pathways is associated with mitochondrial-dependent apoptosis and death receptor dependent apoptosis. Then, transwell invasion, migration, and wound healing assay results proved the inhibition effect by hyperforin in HT29 and HCT116 cells. Additionally, we suggested that hyperforin can effectively inhibit EGFR downstream genes MEK-ERK and AKT signaling, as well as inhibit the phosphorylation of NF-ΚB and the nuclear translocation in CRC cells. In sum, our results show that hyperforin can inhibit the apoptosis and metastasis ability of CRC cells by inhibiting both AKT/NF- ΚB and ERK/NF-ΚB signaling pathway. Citation Format: Ying-Tzu Chen, I-Tsang Chiang, Yuan Chang, Fei-Ting Hsu. Hyperforin induces apoptosis and inhibits invasion via inhibiting AKT/NF-ΚB signaling pathway in colorectal cancer cells. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 4874.