Abstract A020: 1,7-Bis(4-hydroxyphenyl)-4-hepten-3-one from Betula platyphylla impairs autophagy and induces apoptosis in lung cancer cells

Aim of the Study: Betula platyphylla (BP) is a representative medicinal herb used in the treatment of various inflammatory diseases in East Asia. The purpose of this study was to identify the active components of BP extracts and examine the cytotoxic effect of constituents through specific biological mechanisms that regulate the chemotherapeutic activity in lung cancer cells. Materials and Methods: We performed MTT assays, colony formation assays, flow cytometry assays, western blot analysis, and used fluorescence microscopy after transfection with plasmids to study the molecular mechanisms and chemotherapeutic effects of BP extracts and its active components. Results: We observed that BP extracts and 1,7-Bis(4-hydroxyphenyl)-4-hepten-3-one (BE1), one of the components of BP, effectively decreased the cell viability of several lung cancer cell lines. BE1-treated cells exhibited apoptosis induction and cell cycle arrest at the G2/M phase. Further examination demonstrated that BE1 treatment resulted in suppression of autophagy, as evidenced by increased protein expression levels of both LC3 II and p62/SQSTM1. Interestingly, the pharmacological induction of autophagy with rapamycin remarkably reduced the BE1-induced apoptosis, indicating that apoptosis induced by BE1 was associated with autophagy inhibition. Our data also demonstrated that BE1 exposure activated the p38 pathway resulting in regulation of the pro-apoptotic activity. Conclusion: Taken together, we believe that BE1 is a potential anticancer agent for human lung cancer, which exerts its effect by enhancing apoptosis via regulating autophagy and the p38 pathway. Citation Format: Hyun Jin Jung, Ju-Hee Kang, Seung Hyun Oh. 1,7-Bis(4-hydroxyphenyl)-4-hepten-3-one from Betula platyphylla impairs autophagy and induces apoptosis in lung cancer cells [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics; 2019 Oct 26-30; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2019;18(12 Suppl):Abstract nr A020. doi:10.1158/1535-7163.TARG-19-A020