Basic Study
Copyright ©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Apr 21, 2024; 30(15): 2155-2174
Published online Apr 21, 2024. doi: 10.3748/wjg.v30.i15.2155
OSW-1 triggers necroptosis in colorectal cancer cells through the RIPK1/RIPK3/MLKL signaling pathway facilitated by the RIPK1-p62/SQSTM1 complex
Nan Wang, Chao-Yang Li, Teng-Fei Yao, Xiao-Dan Kang, Hui-Shu Guo
Nan Wang, Clinical Laboratory Medicine, The First Affiliated Hospital of Dalian Medical University, Dalian 116023, Liaoning Province, China
Nan Wang, Hui-Shu Guo, The Institute of Integrative Medicine, Dalian Medical University, Dalian 116044, Liaoning Province, China
Chao-Yang Li, Teng-Fei Yao, Xiao-Dan Kang, The Institute of Laboratory Medicine, Dalian Medical University, Dalian 116044, Liaoning Province, China
Hui-Shu Guo, Central Laboratory, The First Affiliated Hospital of Dalian Medical University, Dalian 116011, Liaoning Province, China
Co-first authors: Nan Wang and Chao-Yang Li.
Author contributions: Guo HS designed and supervised the study and drafted the manuscript; Wang N, Li CY, Yao TF and Kang XD performed the experiments; Yao TF and Kang XD analyzed the data; and Wang N and Li CY prepared the manuscript; All the authors have read and approved the final version of the manuscript. The reasons for designating Wang N and Li CY as co-first authors are twofold. Wang N and Li CY completed all the in vitro and in vivo experiments of this study, made the same contribution to this work and share the first authorship. Second, our study was a collaborative effort, and the co-first authorship accurately mirrors the shared responsibilities and collaborative work throughout the study and paper completion. This approach enhances effective communication and facilitates the management of post submission tasks, ultimately contributing to the improved quality and reliability of the paper. In summary, we firmly believe that designating Wang N and Li CY as co-first authors are fitting for our manuscript, as they faithfully represent our team's collaborative spirit, equal contributions, and diversity.
Supported by the Natural Science Foundation of Liaoning Province, No. 2022-MS-330; and Key Projects in Liaoning Province, No. 2020JH2/10300046.
Institutional animal care and use committee statement: All animal experiments conformed to the internationally accepted principles for the care and use of laboratory animals (No. AEE22108, the Ethics Committee of Dalian Medical University).
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
Data sharing statement: No additional data are available.
ARRIVE guidelines statement: The authors have read the ARRIVE guidelines, and the manuscript was prepared and revised according to the ARRIVE guidelines.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Hui-Shu Guo, PhD, Professor, Central Laboratory, The First Affiliated Hospital of Dalian Medical University, No. 222 Zhongshan Road, Dalian 116011, Liaoning Province, China. guohuishu1@126.com
Received: January 5, 2024
Peer-review started: January 5, 2024
First decision: January 22, 2024
Revised: February 2, 2024
Accepted: March 14, 2024
Article in press: March 14, 2024
Published online: April 21, 2024
Processing time: 105 Days and 0.9 Hours
ARTICLE HIGHLIGHTS
Research background

Colorectal cancer (CRC) represents a significant health concern worldwide, and it has severe impacts on human lives. The search for effective drugs is crucial. OSW-1, which is derived from the bulbs of Ornithogalum saundersiae, exhibits potent antitumor properties. However, whether OSW-1 induces necroptosis in CRC cells to exert anticancer effects remains unclear.

Research motivation

We conducted a tandem mass tag proteomic analysis to elucidate the mechanisms underlying necroptosis. We explored the potential for the use of OSW-1 as a drug for the treatment of CRC.

Research objectives

This research aimed to investigate the influence of OSW-1 on CRC cells and elucidate the mechanisms underlying necroptosis.

Research methods

We performed a sequence of functional experiments, including Cell Counting Kit-8 assays and flow cytometry analysis, to assess the inhibitory impact of OSW-1 on CRC cells. We utilized quantitative proteomics to analyze changes in protein expression. transmission electron microscopy (TEM) and immunofluorescence studies were also performed to examine the effects of OSW-1 on necroptosis. Additionally, western blotting, siRNA experiments, and immunoprecipitation were employed to evaluate protein interactions within CRC cells.

Research results

The results revealed a pronounced inhibitory effect of OSW-1 on CRC cells, which was accompanied by a necroptosis-like morphology that was observed via TEM. OSW-1 was shown to trigger necroptosis via activation of the RIPK1/RIPK3/MLKL pathway. Furthermore, the accumulation of p62/SQSTM1 was shown to mediate OSW-1-induced necroptosis through its interaction with RIPK1.

Research conclusions

We propose that OSW-1 can induce necroptosis through the RIPK1/RIPK3/MLKL signaling pathway, which is facilitated by the RIPK1-p62/SQSTM1 complex in CRC cells.

Research perspectives

This study provides a novel mechanism on the antitumor effects of OSW-1 and may provide a new therapeutic target from a new perspective of CRC cell death, which has important clinical significance.