| Residential College | false |
| Status | 已發表Published |
| Formosanin C inhibits non-small-cell lung cancer progression by blocking MCT4/CD147-mediated lactate export | |
| Li, Jiaqi1; Wu, Zongjin1; Chen, Geer1; Wang, Xiaoxuan1; Zhu, Xiaoyu1; Zhang, Yao1; Zhang, Ren1; Wu, Weiyu1; Zhu, Yizhun2; Ma, Lijuan1; Yu, Haijie1 | |
| 2023 | |
| Source Publication | Phytomedicine
 |
| ISSN | 0944-7113 |
| Volume | 109 |
| Abstract | Background: Tumor cells reprogram their metabolic network to maintain their uncontrolled proliferation, metastasis, and resistance to cancer therapy. Treatments targeting abnormal cellular metabolism may have promising therapeutic effects. Formosanin C (FC), a diosgenin derived from the rhizoma of Paris polyphylla var. yunnanensis, has shown potent anti-cancer activities against various cancer types. However, the effect of FC on cancer metabolism remains to be elucidated. Purpose: In this research, we aimed to elucidate FC's effect and potential mechanisms on metabolism in lung cancer. Methods: Colony formation, transwell cell migration, and apoptosis were detected in multiple NSCLC cell lines to assess the cytotoxicity of FC. H NMR metabolomics approach was applied to screen the differential metabolites in H1299 cells and the culture medium. Western blotting, flow cytometry, and other molecular biological techniques were performed to verify the latent mechanism involved in metabolites. An allograft tumor model was employed to investigate the anti-tumor effects of FC in vivo. Results: FC significantly inhibited monoclonal formation and migration and induced cell cycle arrest and apoptosis in NSCLC cells. FC altered the abundances of 12 metabolites in lung cancer cells and 3 metabolites in the medium. These differential metabolites are primarily involved in glycolysis, citric acid cycle, and glutathione pathways. Notably, there was a remarkable increase in intracellular lactate and a reduction in extracellular lactate after FC treatment. Mechanically, FC downregulated the expression of MCT4 and CD147, blocking the export of lactate. Furthermore, FC also evoked mitochondrial dysfunction coupled with excessive oxidative stress, decreased mitochondrial membrane potential, ATP production reduction, glutathione depletion, and Ca overload. Moreover, FC suppressed tumor progression in vivo with reduced protein levels of the MCT4 and CD147 in tumor tissues. Conclusion: FC inhibits lung cancer growth by the novel mechanism in which MCT4/CD147-mediated inhibition of lactate transport and disruption of mitochondrial functions are involved. |
| Keyword | CD147 Formosanin C (FC) Lactate MCT4 NSCLC |
| DOI | 10.1016/j.phymed.2022.154618 |
| URL | View the original |
| Language | 英語English |
| Scopus ID | 2-s2.0-85145720262 |
| Fulltext Access | |
| Citation statistics | |
| Document Type | Journal article |
| Collection | University of Macau |
| Affiliation | 1.Dr. Neher's Biophysics Laboratory for Innovative Drug Discovery, State Key Laboratory of Quality Research in Chinese Medicine, Macau University of Science and Technology, Taipa, Room I01-119, I building, Avenida Wai Long, Macau, China 2.State Key Laboratory of Quality Research in Chinese Medicine, Macau University of Science and Technology, Taipa, Avenida Wai Long, Macau, China |
| First Author Affilication | University of Macau |
| Recommended Citation GB/T 7714 | Li, Jiaqi,Wu, Zongjin,Chen, Geer,et al. Formosanin C inhibits non-small-cell lung cancer progression by blocking MCT4/CD147-mediated lactate export[J]. Phytomedicine, 2023, 109. |
| APA | Li, Jiaqi., Wu, Zongjin., Chen, Geer., Wang, Xiaoxuan., Zhu, Xiaoyu., Zhang, Yao., Zhang, Ren., Wu, Weiyu., Zhu, Yizhun., Ma, Lijuan., & Yu, Haijie (2023). Formosanin C inhibits non-small-cell lung cancer progression by blocking MCT4/CD147-mediated lactate export. Phytomedicine, 109. |
| MLA | Li, Jiaqi,et al."Formosanin C inhibits non-small-cell lung cancer progression by blocking MCT4/CD147-mediated lactate export".Phytomedicine 109(2023). |
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