Cyclohexene oxide CA, a derivative of zeylenone, exhibits anti-cancer activity in glioblastoma by inducing G0/G1 phase arrest through interference with EZH2

• DOI: 10.3389/fphar.2023.1326245
• Publication Date: 2024-01-09T04:13:35Z
• Authors: Rui Su; Weiwei Cao; Guoxu Ma; Weiping Li; Zongyang Li; Yongpei Liu; Lei Chen; Zebin Chen; Xuejuan Li; Ping Cui; Guodong Huang
• Keywords: Derivative (finance)

Introduction: Due to its highly aggressiveness and malignancy, glioblastoma (GBM) urgently requires a safe effective treatment strategy. Zeylenone, natural polyoxygenated cyclohexenes compound isolated from Uvaria grandiflora , has exhibited potential biological activities in various human diseases, including tumors. Methods: We designed synthesized series of (+)-Zeylenone analogues evaluated their anti-GBM roles through structural-activity analysis. Cell Counting Kit-8, TUNEL, transwell flow cytometry were employed for investigating the anticancer effects CA on GBM cells. Western blotting, molecular docking, qRT-PCR ChIP assays performed reveal underlying mechanisms by which regulates cell cycle. The nude mouse xenograft model, HE staining, immunohistochemistry was used evaluate effect vivo . Results: identified ((1R, 2R, 3S)-3-p-fluorobenzoyl-zeylenone) as having lowest IC 50 value significantly inhibited malignant behaviors cells induced G0/G1 phase arrest vitro Furthermore, we validated mechanism interferes with EZH2, attenuating down-regulation cyclin-dependent kinase inhibitors p27 p16 PRC2 complex. By establishing orthotopic mice models, further inhibitory role tumorigenesis values synergistically potentiate anti-tumor EZH2 inhibitors. Conclusion: Overall, this paper elucidated CA, may provide therapeutic drug candidate treatment.