OSW-1 triggers necroptosis in colorectal cancer cells through the RIPK1/RIPK3/MLKL signaling pathway facilitated by the RIPK1- p62/SQSTM1 complex

作     者：Nan Wang Chao-Yang Li Teng-Fei Yao Xiao-Dan Kang Hui-Shu Guo 

作者机构：Clinical Laboratory MedicineThe First Affiliated Hospital of Dalian Medical UniversityDalian 116023Liaoning ProvinceChina The Institute of Integrative MedicineDalian Medical UniversityDalian 116044Liaoning ProvinceChina The Institute of Laboratory MedicineDalian Medical UniversityDalian 116044Liaoning ProvinceChina Central LaboratoryThe First Affiliated Hospital of Dalian Medical UniversityDalian 116011Liaoning ProvinceChina 

出 版 物：《World Journal of Gastroenterology》 (世界胃肠病学杂志（英文版）)

年 卷 期：2024年第30卷第15期

页      面：2155-2174页

核心收录：

学科分类：1008[医学-中药学(可授医学、理学学位)] 1006[医学-中西医结合] 1002[医学-临床医学] 100602[医学-中西医结合临床] 10[医学] 

基　　金：Supported by the Natural Science Foundation of Liaoning Province,No.2022-MS-330 and Key Projects in Liaoning Province,No.2020JH2/10300046 

主　　题：OSW-1 Necroptosis RIPK1 P62/SQSTM1 Colorectal cancer 

摘      要：BACKGROUND Necroptosis has emerged as a novel molecular pathway that can be targeted by chemotherapy agents in the treatment of ***-1,which is derived from the bulbs of Ornithogalum saundersiae Baker,exerts a wide range of pharmaco-logical *** To explore whether OSW-1 can induce necroptosis in colorectal cancer(CRC)cells,thereby expanding its range of clinical *** We performed a sequence of functional experiments,including Cell Counting Kit-8 assays and flow cytometry analysis,to assess the inhibitory effect of OSW-1 on CRC *** utilized quantitative proteomics,employing tandem mass tag label-ing combined with liquid chromatography-tandem mass spectrometry,to analyze changes in protein *** bioinformatic analysis was conducted to elucidate the biological processes associated with the identified *** electron microscopy(TEM)and immunofluorescence studies were also performed to examine the effects of OSW-1 on ***,western blotting,siRNA experiments,and immunoprecipitation were employed to evaluate protein interactions within CRC *** The results revealed that OSW-1 exerted a strong inhibitory effect on CRC cells,and this effect was accompanied by a necroptosis-like morphology that was observable via ***-1 was shown to trigger necroptosis via activation of the RIPK1/RIPK3/MLKL ***,the accumulation of p62/SQSTM1 was shown to mediate OSW-1-induced necroptosis through its interaction with *** We propose that OSW-1 can induce necroptosis through the RIPK1/RIPK3/MLKL signaling pathway,and that this effect is mediated by the RIPK1-p62/SQSTM1 complex,in CRC *** results provide a theoretical foundation for the use of OSW-1 in the clinical treatment of CRC.