Cyclobrachycoumarin from Gerbera piloselloides Inhibits Colorectal Cancer In Vitro and In Vivo

• Published in: Molecules (Basel, Switzerland) Switzerland), 2024-11, Vol.29 (23), p.5678
• Main Authors: Fan, Limei, Ye, Xiansheng, Fang, Qian, Li, Xiaoxuan, Wang, Haiping, Sun, Binlian, Shu, Xiji, Hou, Xiaoying, Liu, Yuchen
• Format: Article
• Language: English
• Subjects: Animals; Antineoplastic Agents, Phytogenic - chemistry; Antineoplastic Agents, Phytogenic - pharmacology; Apoptosis; Apoptosis - drug effects; Asteraceae - chemistry; Cancer; Cancer therapies; Cell cycle; Cell growth; Cell Line, Tumor; Cell Proliferation - drug effects; Chemotherapy; Chinese medicine; Chromatography; Colorectal cancer; Colorectal Neoplasms - drug therapy; Colorectal Neoplasms - metabolism; Colorectal Neoplasms - pathology; Coumarins; Coumarins - chemistry; Coumarins - pharmacology; cyclobrachycoumarin; Gerbera piloselloides; Health aspects; High performance liquid chromatography; Humans; Investigations; Liu, Timothy; Medicinal plants; Medicine, Botanic; Medicine, Herbal; Mice; Plant Extracts - chemistry; Plant Extracts - pharmacology; Prevention; Toxicity; Tumors; Xenograft Model Antitumor Assays
• ISSN: 1420-3049; 1420-3049
• DOI: 10.3390/molecules29235678

, a plant in the family, is a traditional Chinese medicinal herb known for its unique therapeutic properties, including reported anti-tumor and antioxidant effects. Recent studies suggest that the main constitute of , coumarins, may have potential anti-tumor activity. Recent research suggests that coumarins, the active compounds in , may hold potential anti-tumor activity. However, the pharmacodynamic constituents remain unidentified. This study aims to isolate and characterize the bioactive compounds of and to assess its anti-tumor effects. Initially, seven compounds, including coumarins, a ketone, and a furanolide, were isolated and identified from by semi-preparative high-performance liquid chromatography (HPLC) and nuclear magnetic resonance (NMR) analysis. The anti-tumor effects of these compounds were evaluated across four different cancer cell lines. Among them, the compound cyclobrachycoumarin showed a significant inhibitory effect on colorectal cancer (CRC) cell proliferation and was selected for further investigation. Cyclobrachycoumarin was found to induce CRC cell apoptosis and cell cycle arrest in a dose-dependent manner. This treatment also led to increased levels of ROS and cleaved PARP, along with decreased expressions of survivin, cyclin D1, and CDK1. In vivo studies further demonstrated that cyclobrachycoumarin effectively reduced tumor growth in HT-29 xenograft models by promoting apoptosis and cell cycle arrest, with a favorable tolerability profile. In summary, this study suggests that cyclobrachycoumarin may be a promising candidate for safe and effective CRC therapy.