JZUS - Journal of Zhejiang University SCIENCE

Journal of Zhejiang University SCIENCE B

Accepted manuscript available online (unedited version)

Momordicine I induces ER stress and inhibits OSCC by targeting ribosomal proteins

Author(s): Jianlu KONG, Ziyu ZHU, Yijie HU, Siyi ZHOU, Tianyi GU, Xiao SHEN, Huiming WANG, Mengfei YU, Yu LIU
Affiliation(s): Stomatology Hospital, School of Stomatology, Zhejiang University School of Medicine, Zhejiang Provincial Clinical Research Center for Oral Diseases, Key Laboratory of Oral Biomedical Research of Zhejiang Province, Cancer Center of Zhejiang University, Hangzhou 310006, China; more
Corresponding email(s): 7514061@zju.edu.cn, whmwhm@zju.edu.cn
Key Words: Oral squamous cell carcinoma (OSCC); Momordicine I (MI); Endoplasmic Reticulum (ER) stress; Ribosomal proteins

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Jianlu KONG, Ziyu ZHU, Yijie HU, Siyi ZHOU, Tianyi GU, Xiao SHEN, Huiming WANG, Mengfei YU, Yu LIU. Momordicine I induces ER stress and inhibits OSCC by targeting ribosomal proteins[J]. Journal of Zhejiang University Science B,in press.Frontiers of Information Technology & Electronic Engineering,in press.https://doi.org/10.1631/jzus.B2500142

@article{title="Momordicine I induces ER stress and inhibits OSCC by targeting ribosomal proteins",
author="Jianlu KONG, Ziyu ZHU, Yijie HU, Siyi ZHOU, Tianyi GU, Xiao SHEN, Huiming WANG, Mengfei YU, Yu LIU",
journal="Journal of Zhejiang University Science B",
year="in press",
publisher="Zhejiang University Press & Springer",
doi="https://doi.org/10.1631/jzus.B2500142"
}

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%T Momordicine I induces ER stress and inhibits OSCC by targeting ribosomal proteins
%A Jianlu KONG
%A Ziyu ZHU
%A Yijie HU
%A Siyi ZHOU
%A Tianyi GU
%A Xiao SHEN
%A Huiming WANG
%A Mengfei YU
%A Yu LIU
%J Journal of Zhejiang University SCIENCE B
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%@ 1673-1581
%D in press
%I Zhejiang University Press & Springer
doi="https://doi.org/10.1631/jzus.B2500142"

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T1 - Momordicine I induces ER stress and inhibits OSCC by targeting ribosomal proteins
A1 - Jianlu KONG
A1 - Ziyu ZHU
A1 - Yijie HU
A1 - Siyi ZHOU
A1 - Tianyi GU
A1 - Xiao SHEN
A1 - Huiming WANG
A1 - Mengfei YU
A1 - Yu LIU
J0 - Journal of Zhejiang University Science B
SP -
EP -
%@ 1673-1581
Y1 - in press
PB - Zhejiang University Press & Springer
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doi="https://doi.org/10.1631/jzus.B2500142"

Abstract
Chinese Summary
Academic Network
Reviewer Comment

Abstract: Oral squamous cell carcinoma (OSCC) is one of the most common malignant tumors worldwide. This necessitates the development of innovative drugs with high efficiency, low toxicity, and good tolerance. Bitter melon extract has been reported to have potent anticancer activity against OSCC. We evaluated the effects of nine triterpenoids from bitter melon extract on OSCC using CCK8 proliferation and Transwell migration assays. Among the nine triterpenoids, momordicine I (MI) exhibited the strongest anticancer activity against OSCC. Animal experiments also showed that MI inhibited OSCC cell growth in vivo. Additionally, MI decreased the mitochondrial membrane potential and promoted apoptosis in OSCC. RNA-seq analysis revealed that MI induced an unfolded protein response (UPR) and endoplasmic reticulum (ER) stress, which was confirmed by western blotting and RT-qPCR. Cellular thermal shift assay (CETSA) and mass spectrometry (MS) analysis, combined with molecular docking, identified ribosomal proteins (RPL7, RPL11, RPL12, RPL18, RPL30, RPL38, RPS13, RPS25) as MI targets. By targeting ribosomal proteins, MI likely disrupts ribosome-mediated protein folding, leading to UPR and ER stress. In summary, MI targets ribosomal proteins to induce ER stress and inhibit OSCC, highlighting its therapeutic potential.

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