ORIGINAL RESEARCH article
Front. Oncol.
Sec. Cancer Molecular Targets and Therapeutics
This article is part of the Research TopicThe Ubiquitin-Proteasome System and Cellular Signaling: Mechanisms and Regulatory Roles in Cancer and Infectious Diseases.View all 4 articles
Mebendazole inhibits PELI3-mediated ubiquitination of TRADD in non-small cell lung cancer cells
Provisionally accepted
Fannian Li1
Xiaoning Li2Haitao Li3Shuai Li3
Yanchao Liu3Xianhua Bai3Tianjie Qi3Xiumin Zhao3
Yuzheng He3*- 1the First Affiliated Hospital of Xing Tai Medical College, Xing Tai, China
- 2Hebei General Hospital, Hebei, China
- 3Second Hospital of Hebei Medical University, Shijiazhuang, China
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Introduction: Tumor necrosis factor receptor 1-associated death domain protein (TRADD) can trigger proapoptotic autophagy in non-small cell lung cancer (NSCLC). While the potential ubiquitin-protein ligase (E3) against TRADD is not well deciphered. Methods: UbiBrowser was used to predict the potential E3 ubiquitin ligase to bind with TRADD. Co-immunoprecipitation was performed in HEK293T cells co-transfected with Myc-PELI3, Flag-TRADD, or HA-Ub plasmids. Increasing doses of Myc-PELI3 were transfected into HCC827 and A549 cells, and the relative expression of TRADD was detected. Cycloheximide chase assay was performed in A549 cells transfected with Myc-PELI3 plasmids, and the stability of TRADD was revealed. CCK-8 assay was performed in A549 and HCC827 cells incubated with increasing doses of Mebendazole. The expression of TRADD and PELI3 after Mebendazole incubation was assayed with Western Blot and RT-PCR. The potential E3 ubiquitin ligase of PELI3 was predicted by the UbiBrowser platform, and the binding of PELI3 with TRADD was testified in HEK293T cells co-transfected with Myc-PELI3 and Flag-TRADD plasmids. Results: PELI3 overexpression diminished the relative protein expression of TRADD, while not affecting the relative mRNA expression in both A549 and HCC827 cells. Cycloheximide assay and following HA-Ub detection demonstrated that PELI3 decreased the protein stability of TRADD by inducing polyubiquitination. Mebendazole inhibited the viability of HCC827 and A549 cells with diminished expression of PELI3 and increased expression of TRADD. Conclusions: PELI3 can function as an E3 ubiquitin ligase to ubiquitinate TRADD, and Mebendazole might be a promising drug to affect PELI3 expression in NSCLC.
Keywords: E3 ubiquitin ligase, Mebendazole, Non-small cell lung cancer, PELI3, TRADD
Received: 23 Oct 2025; Accepted: 16 Dec 2025.
Copyright: © 2025 Li, Li, Li, Li, Liu, Bai, Qi, Zhao and He. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Yuzheng He
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