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

Jianlu KONG; Ziyu ZHU; Yijie HU; Siyi ZHOU; Tianyi GU; Xiao SHEN; Huiming WANG; Mengfei YU; Yu LIU

doi:10.1631/jzus.B2500142

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

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Research Article | Updated：2026-02-06

Momordicine I induces ER stress and inhibits OSCC by targeting ribosomal proteins
Momordicine I induces ER stress and inhibits OSCC by targeting ribosomal proteins
苦瓜素I通过靶向核糖体蛋白诱导内质网应激抑制口腔鳞状细胞癌
Journal of Zhejiang University-SCIENCE B Vol. 27, Issue 2, Pages: 164-180(2026)
Affiliations：

1.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
2.The Second School of Clinical Medicine, Zhejiang Chinese Medical University, Hangzhou 310053, China
Funds：
DOI：10.1631/jzus.B2500142
CLC：
CSTR：
Received：25 March 2025，

Revised：2025-09-10，

Online First：22 December 2025，

Published：06 February 2026
Accepted：

孔建鲁,朱子羽,胡屹杰等.苦瓜素I通过靶向核糖体蛋白诱导内质网应激抑制口腔鳞状细胞癌[J].浙江大学学报（英文版）（B辑：生物医学和生物技术）,2026,27(02):164-180.

Jianlu KONG, Ziyu ZHU, Yijie HU, et al. Momordicine I induces ER stress and inhibits OSCC by targeting ribosomal proteins[J]. Journal of Zhejiang University-SCIENCE B, 2026, 27(2): 164-180.
孔建鲁,朱子羽,胡屹杰等.苦瓜素I通过靶向核糖体蛋白诱导内质网应激抑制口腔鳞状细胞癌[J].浙江大学学报（英文版）（B辑：生物医学和生物技术）,2026,27(02):164-180. DOI： 10.1631/jzus.B2500142.

Jianlu KONG, Ziyu ZHU, Yijie HU, et al. Momordicine I induces ER stress and inhibits OSCC by targeting ribosomal proteins[J]. Journal of Zhejiang University-SCIENCE B, 2026, 27(2): 164-180. DOI： 10.1631/jzus.B2500142.

摘要

口腔鳞状细胞癌（OSCC）是全球最常见的恶性肿瘤之一，目前亟需开发高效、低毒且耐受性良好的创新药物。据报道，苦瓜提取物对OSCC具有显著的抗癌活性。在本研究中，我们采用细胞计数试剂盒-8（CCK-8）增殖实验和Transwell迁移实验评估了苦瓜提取物中九种三萜类化合物对OSCC的影响。结果显示，苦瓜素I（MI）在九种化合物中表现出最强的抗OSCC活性。进一步的动物实验也证实，MI在体内能抑制OSCC细胞的生长。此外，MI可降低线粒体膜电位并促进OSCC细胞的凋亡。通过RNA 测序（RNA-seq）分析发现，MI能诱导未折叠蛋白反应（UPR）和内质网（ER）应激，这一结果经蛋白质印迹（western blotting）和实时荧光定量逆转录聚合酶链反应（RT-qPCR）验证得到确认。随后，我们联合细胞热位移分析（CETSA）、质谱（MS）分析及分子对接技术，鉴定出核糖体蛋白（RPL7、RPL11、RPL12、RPL18、RPL30、RPL38、RPS13和RPS25）是MI的作用靶点。我们推测，MI通过靶向核糖体蛋白，能够破坏核糖体介导的蛋白质折叠，从而引发UPR和ER应激。综上，MI通过靶向核糖体蛋白诱导ER应激抑制OSCC细胞的生长，表明其具有良好的治疗潜力。

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 cell counting kit-8 (CCK-8) 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-sequencing (RNA-seq) analysis revealed that MI induced an unfolded protein response (UPR) and endoplasmic reticulum (ER) stress

which was confirmed by western blotting and reverse transcription-quantitative polymerase chain reaction (RT-qPCR). Cellular thermal shift assay (CETSA) and mass spectrometry (MS) analysis

combined with molecular docking

identified ribosomal proteins (ribosomal protein L7 (RPL7)

RPL11

RPL12

RPL18

RPL30

RPL38

RPS13

and RPS25) as MI targets. By targeting ribosomal proteins

MI likely disrupts ribosome-mediated protein folding

leading to the UPR and ER stress. In summary

MI targets ribosomal proteins to induce ER stress and inhibit OSCC

highlighting its therapeutic potential.

关键词

Keywords

references

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Related Institution

Department of Oral and Maxillofacial Surgery, Center of Stomatology, Xiangya Hospital, Central South University

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National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University

Department of Oral and Maxillofacial Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine

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