1. The Active Fraction of Polyrhachis vicina Roger (AFPR) activates ERK to cause necroptosis in colorectal cancer.
- Author
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Li, Dong-mei, Zhu, Fu-cui, Wei, Jie, Xie, Jia-xiu, He, Jun-hui, Wei, Dong-mei, Li, Yi, Lai, Ke-dao, Liu, Li-min, Su, Qi-biao, Wei, Gui-ning, Wang, Bin, and Liu, Yan-cheng
- Subjects
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REVERSE transcriptase polymerase chain reaction , *STAINS & staining (Microscopy) , *CARCINOGENESIS , *WESTERN immunoblotting , *ANTINEOPLASTIC agents , *RNA , *COLORECTAL cancer , *CELLULAR signal transduction , *ARTHROPODA , *TREATMENT effectiveness , *TRANSFERASES , *INSECTS , *PHARMACEUTICAL chemistry , *COMPUTER-assisted molecular modeling , *CELL death , *CHINESE medicine , *PHARMACODYNAMICS - Abstract
Polyrhachis vicina Roger (P. vicina), a traditional Chinese medicinal animal, has been used to treat rheumatoid arthritis, hepatitis, cancer, and other conditions. Due to its anti-inflammatory properties, our previous pharmacological investigations have demonstrated that it is effective against cancer, depression, and hyperuricemia. Nevertheless, the key active components and targets of P. vicina in cancers are still unexplored. The study aimed to evaluate the pharmacological treatment mechanism of the active fraction of P. vicina (AFPR) in treating colorectal cancer (CRC) and to further reveal its active ingredients and key targets. To examine the inhibitory impact of AFPR on CRC growth, tumorigenesis assays, cck-8 assays, colony formation assays, and MMP detection were utilized. The primary components of AFPR were identified by GC-MS analysis. The network pharmacology, molecular docking, qRT-PCR, western blotting, CCK-8 assays, colony formation assay, Hoechst staining, Annexin V-FITC/PI double staining, and MMP detection were performed to pick out the active ingredients and potential key targets of AFPR. The function of Elaidic acid on necroptosis was investigated through siRNA interference and the utilization of inhibitors. Elaidic acid's effectiveness to suppress CRC growth in vivo was assessed using a tumorigenesis experiment. Studies confirmed that AFPR prevented CRC from growing and evoked cell death. Elaidic acid was the main bioactive ingredient in AFPR that targeted ERK. Elaidic acid greatly affected the ability of SW116 cells to form colonies, produce MMP, and undergo necroptosis. Additionally, Elaidic acid promoted necroptosis predominantly by activating ERK/RIPK1/RIPK3/MLKL. According to our findings, Elaidic acid is the main active component of AFPR, which induced necroptosis in CRC through the activation of ERK. It represents a promising alternative therapeutic option for CRC. This work provided experimental support for the therapeutic application of P. vicina Roger in the treatment of CRC. [Display omitted] • The active fraction of Polyrhachis vicina Roger (AFPR) inhibited CRC growth in vivo and in vitro. • Network pharmacology and molecular docking predicted ERK might be the key target of AFPR in antagonizing CRC. • Elaidic acid was a key active component of AFPR and induced necroptosis. • Elaidic acid induced necroptosis via ERK activation. [ABSTRACT FROM AUTHOR]
- Published
- 2023
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