Abstract 6323: Cancer chemopreventive effects and mechanisms of <i>Citrus depressa</i> leaf extracts

Many diseases such as cancer are closely linked to excessive intracellular oxidative stress and chronic inflammatory responses. Studies have demonstrated that dietary interventions can mitigate or prevent the progression of certain chronic diseases, which reinforces the significance of the 'prevention is better than cure' concept. This study evaluated the antioxidant capacity and chemopreventive mechanisms of Citrus depressa leaf (CDL) extracts in mouse JB6 P+ skin cells in inhibiting carcinogenesis induced by the tumor promoter 12-O-tetradecanoylphorbol-13-acetate (TPA). The preparation of various solvent extracts from CDL revealed a richness in flavonoids, which are key bioactive compounds commonly found in citrus fruits. CDL-WE (water extract) and CDL-95EE (95% ethanolic extract) (5-40 μg/mL) both effectively prevented the anchorage-independent growth of JB6 P+ cells with minimal cytotoxicity, but CDL-95EE was found to have superior effects. In addition, CDL-95EE promoted the expression of UGT1A and HO-1 enzymes at the protein level, enhanced the expression of Nrf2 pathway-related genes in mRNA, and decreased TPA-related ROS levels. The protein expression of DNA methyltransferases (DNMTs) and histone deacetylases (HDACs) was also reduced by CDL-95EE, which indicates that it is involved in epigenetic regulation. These findings demonstrate the chemopreventive capacity of CDL and endorse their use in creating agricultural byproducts from this resource. Citation Format: Zheng-Yuan Su, Hsin-Yu Chiang. Cancer chemopreventive effects and mechanisms of Citrus depressa leaf extracts [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 6323.