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薯蓣皂苷通过靶向BMI1-Noxa轴诱导口腔鳞状细胞癌细胞凋亡。

Targeting the BMI1-Noxa axis by Dioscin induces apoptosis in oral squamous cell carcinoma cells.

作者信息

Fang Jinglin, Wang Ruirui, Li Xiaoying, Wang XiaoCong, Gong Lingling, Lou An, Lu Jie, Zhang Xiaoyue, Zhao Qin, Yu Xinfang, Zhou Qiling, Li Ming

机构信息

School of Stomatology, Hunan University of Chinese Medicine, Changsha, Hunan 410208, China.

Changsha Stomatological Hospital, Changsha, Hunan 410004, China.

出版信息

J Cancer. 2025 Jan 1;16(1):110-121. doi: 10.7150/jca.100631. eCollection 2025.

DOI:10.7150/jca.100631
PMID:39744574
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11660131/
Abstract

Dioscin is a natural plant-derived steroidal saponin that exerts antitumor effects in multiple cancers. It is widely involved in multiple apoptotic pathways and exerts its anti-tumor effects. In this study, we discovered that Dioscin treatment increased the expression of Noxa, thereby inducing the apoptosis of OSCC cells. Previous reports indicate that dysfunction of the BMI1-Noxa axis is frequently observed in multiple cancers. Our study revealed that Dioscin upregulates Noxa by impairing the protein expression of BMI1 in OSCC cells. Dioscin promotes the ubiquitination of BMI1 and facilitates its degradation, leading to upregulation of Noxa expression at the mRNA level and activation of apoptosis. Additionally, Dioscin exhibited potent tumor suppression in xenograft tumor models. In conclusion, our research provides new insights and strategies for inhibiting OSCC cells by investigating the ant-tumor mechanism of the natural compound Dioscin.

摘要

薯蓣皂苷是一种天然植物来源的甾体皂苷，在多种癌症中发挥抗肿瘤作用。它广泛参与多种凋亡途径并发挥其抗肿瘤作用。在本研究中，我们发现薯蓣皂苷处理可增加Noxa的表达，从而诱导口腔鳞状细胞癌（OSCC）细胞凋亡。先前的报道表明，BMI1-Noxa轴功能障碍在多种癌症中经常出现。我们的研究表明，薯蓣皂苷通过损害OSCC细胞中BMI1的蛋白表达来上调Noxa。薯蓣皂苷促进BMI1的泛素化并促进其降解，导致Noxa表达在mRNA水平上调并激活凋亡。此外，薯蓣皂苷在异种移植肿瘤模型中表现出强大的肿瘤抑制作用。总之，我们的研究通过研究天然化合物薯蓣皂苷的抗肿瘤机制，为抑制OSCC细胞提供了新的见解和策略。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c19c/11660131/ad3fa0db9795/jcav16p0110g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c19c/11660131/0dd8257cda86/jcav16p0110g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c19c/11660131/a139104dd074/jcav16p0110g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c19c/11660131/43ae4aad79c1/jcav16p0110g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c19c/11660131/e4f87393688b/jcav16p0110g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c19c/11660131/65f1e8c09f95/jcav16p0110g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c19c/11660131/ad3fa0db9795/jcav16p0110g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c19c/11660131/0dd8257cda86/jcav16p0110g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c19c/11660131/a139104dd074/jcav16p0110g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c19c/11660131/43ae4aad79c1/jcav16p0110g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c19c/11660131/e4f87393688b/jcav16p0110g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c19c/11660131/65f1e8c09f95/jcav16p0110g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c19c/11660131/ad3fa0db9795/jcav16p0110g006.jpg

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本文引用的文献

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Anti-papillary thyroid carcinoma effects of dioscorea bulbifera L. through ferroptosis and the PI3K/AKT pathway based on network pharmacology and experimental validation.基于网络药理学和实验验证的盾叶薯蓣通过铁死亡和 PI3K/AKT 通路对甲状腺癌的抗作用。
J Ethnopharmacol. 2024 May 23;326:117912. doi: 10.1016/j.jep.2024.117912. Epub 2024 Feb 20.
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Dioscin: Therapeutic potential for diabetes and complications.薯蓣皂苷：治疗糖尿病及其并发症的潜力。
Biomed Pharmacother. 2024 Jan;170:116051. doi: 10.1016/j.biopha.2023.116051. Epub 2023 Dec 28.
3
Dioscin Impedes Proliferation, Metastasis and Enhances Autophagy of Gastric Cancer Cells via Regulating the USP8/TGM2 Pathway.
薯蓣皂苷通过调节 USP8/TGM2 通路抑制胃癌细胞的增殖、转移并增强自噬。
Mol Biotechnol. 2024 Dec;66(12):3700-3711. doi: 10.1007/s12033-023-00978-7. Epub 2023 Dec 12.
4
Oral squamous cell carcinomas: state of the field and emerging directions.口腔鳞状细胞癌：研究现状与新兴方向。
Int J Oral Sci. 2023 Sep 22;15(1):44. doi: 10.1038/s41368-023-00249-w.
5
Tanshinone IIA inhibits cell viability and promotes PUMA-mediated apoptosis of oral squamous cell carcinoma.丹参酮IIA抑制口腔鳞状细胞癌的细胞活力并促进PUMA介导的细胞凋亡。
J Cancer. 2023 Aug 6;14(13):2481-2490. doi: 10.7150/jca.84537. eCollection 2023.
6
Gastrodin destabilizes survivin and overcomes pemetrexed resistance.天麻素使survivin 不稳定并克服培美曲塞耐药性。
Cell Signal. 2023 Oct;110:110851. doi: 10.1016/j.cellsig.2023.110851. Epub 2023 Aug 14.
7
Dioscin Ameliorates Experimental Autoimmune Thyroiditis via the mTOR and TLR4/NF-κB Signaling.薯蓣皂苷通过 mTOR 和 TLR4/NF-κB 信号通路改善实验性自身免疫性甲状腺炎。
Drug Des Devel Ther. 2023 Aug 2;17:2273-2285. doi: 10.2147/DDDT.S410901. eCollection 2023.
8
Dioscin inhibiting EGFR-mediated Survivin expression promotes apoptosis in oral squamous cell carcinoma cells.薯蓣皂苷抑制EGFR介导的Survivin表达促进口腔鳞状细胞癌细胞凋亡。
J Cancer. 2023 Jul 9;14(11):2027-2038. doi: 10.7150/jca.85011. eCollection 2023.
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Dioscin modulates macrophages polarization and MDSCs differentiation to inhibit tumorigenesis of colitis-associated colorectal cancer.薯蓣皂苷通过调节巨噬细胞极化和 MDSCs 分化抑制结肠炎相关结直肠癌的发生。
Int Immunopharmacol. 2023 Apr;117:109839. doi: 10.1016/j.intimp.2023.109839. Epub 2023 Feb 19.
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