Baicalein induces apoptosis by inhibiting the glutamine-mTOR metabolic pathway in lung cancer
Introduction: Baicalein, a bioactive component of Scutellaria baicalensis Georgi, has been shown to promote apoptosis in non-small cell lung cancer cells. However, previous studies have not determined if baicalein exerts proapoptotic effects by modulating the metabolic pathways. Objective: To invest...
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Elsevier
2025-02-01
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| Series: | Journal of Advanced Research |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2090123224000857 |
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| author | Jingyang Li Di Zhang Shaohui Wang Peng Yu Jiayi Sun Yi Zhang Xianli Meng Juan Li Li Xiang |
| author_facet | Jingyang Li Di Zhang Shaohui Wang Peng Yu Jiayi Sun Yi Zhang Xianli Meng Juan Li Li Xiang |
| author_sort | Jingyang Li |
| collection | DOAJ |
| description | Introduction: Baicalein, a bioactive component of Scutellaria baicalensis Georgi, has been shown to promote apoptosis in non-small cell lung cancer cells. However, previous studies have not determined if baicalein exerts proapoptotic effects by modulating the metabolic pathways. Objective: To investigate if baicalein induces apoptosis in lung cancer cells by modulating the glutamine-mTOR metabolic pathway. Methods: The in vivo anti-lung cancer activity of baicalein (50, 100, and 200 mg/kg) was evaluated using a xenograft model. In vitro experiments were used to assess the efficacy of baicalein (for H1299: 12.5, 25, and 50 μM; for A549: 10, 20, and 40 μM) on lung cancer cell proliferation, colony formation, and apoptosis. Metabolomics analysis was performed using liquid chromatography-mass spectrometry. The binding of baicalein to glutamine transporters and glutaminase was examined using molecular docking. The overexpression of glutamine transporters was validated using qRT–PCR and western blot analyses. The levels of ASCT2, LAT1, GLS1, p-mTOR, mTOR, and apoptosis-related proteins were evaluated using western blot analysis. Results: Baicalein inhibited lung cancer xenograft tumor growth in vivo and suppressed proliferation and promoted apoptosis in lung cancer cells in vitro. Additionally, baicalein altered amino acid metabolites, especially glutamine metabolites, in H1299 and A549 cells. Mechanistically, baicalein interacted with glutamine transporters as well as glutaminase and inhibited their activation. The expression of mTOR, an apoptosis-related protein and downstream target of glutamine metabolism, was also inhibited by baicalein treatment. Importantly, we next demonstrated the suppression of mTOR signaling and the induction of apoptosis by baicalein were achieved by regulating glutamine metabolism. Conclusion: Baicalein inhibited the mTOR signaling pathway and induced apoptosis by downregulating glutamine metabolism. The potential of baicalein to induce apoptosis in lung cancer cells by selectively targeting the glutamine-mTOR pathway suggests an encouraging approach for treating lung cancer. |
| format | Article |
| id | doaj-art-2ed9d5ff64a34c2bb8d7cac71b618c81 |
| institution | Kabale University |
| issn | 2090-1232 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Journal of Advanced Research |
| spelling | doaj-art-2ed9d5ff64a34c2bb8d7cac71b618c812025-01-18T05:04:21ZengElsevierJournal of Advanced Research2090-12322025-02-0168341357Baicalein induces apoptosis by inhibiting the glutamine-mTOR metabolic pathway in lung cancerJingyang Li0Di Zhang1Shaohui Wang2Peng Yu3Jiayi Sun4Yi Zhang5Xianli Meng6Juan Li7Li Xiang8State Key Laboratory of Southwestern Chinese Medicine Resources, School of Pharmacy, Innovative Institute of Chinese Medicine and Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, ChinaState Key Laboratory of Southwestern Chinese Medicine Resources, School of Pharmacy, Innovative Institute of Chinese Medicine and Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, ChinaState Key Laboratory of Southwestern Chinese Medicine Resources, School of Pharmacy, Innovative Institute of Chinese Medicine and Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, ChinaState Key Laboratory of Southwestern Chinese Medicine Resources, School of Pharmacy, Innovative Institute of Chinese Medicine and Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, ChinaState Key Laboratory of Southwestern Chinese Medicine Resources, School of Pharmacy, Innovative Institute of Chinese Medicine and Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, ChinaState Key Laboratory of Southwestern Chinese Medicine Resources, School of Pharmacy, Innovative Institute of Chinese Medicine and Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, ChinaState Key Laboratory of Southwestern Chinese Medicine Resources, School of Pharmacy, Innovative Institute of Chinese Medicine and Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China; Corresponding authors.Sichuan Clinical Research Center for Cancer, Sichuan Cancer Hospital & Institute, Sichuan Cancer Center, Affiliated Cancer Hospital of University of Electronic Science and Technology of China, Chengdu 610041, China; Corresponding authors.State Key Laboratory of Southwestern Chinese Medicine Resources, School of Pharmacy, Innovative Institute of Chinese Medicine and Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China; Corresponding authors.Introduction: Baicalein, a bioactive component of Scutellaria baicalensis Georgi, has been shown to promote apoptosis in non-small cell lung cancer cells. However, previous studies have not determined if baicalein exerts proapoptotic effects by modulating the metabolic pathways. Objective: To investigate if baicalein induces apoptosis in lung cancer cells by modulating the glutamine-mTOR metabolic pathway. Methods: The in vivo anti-lung cancer activity of baicalein (50, 100, and 200 mg/kg) was evaluated using a xenograft model. In vitro experiments were used to assess the efficacy of baicalein (for H1299: 12.5, 25, and 50 μM; for A549: 10, 20, and 40 μM) on lung cancer cell proliferation, colony formation, and apoptosis. Metabolomics analysis was performed using liquid chromatography-mass spectrometry. The binding of baicalein to glutamine transporters and glutaminase was examined using molecular docking. The overexpression of glutamine transporters was validated using qRT–PCR and western blot analyses. The levels of ASCT2, LAT1, GLS1, p-mTOR, mTOR, and apoptosis-related proteins were evaluated using western blot analysis. Results: Baicalein inhibited lung cancer xenograft tumor growth in vivo and suppressed proliferation and promoted apoptosis in lung cancer cells in vitro. Additionally, baicalein altered amino acid metabolites, especially glutamine metabolites, in H1299 and A549 cells. Mechanistically, baicalein interacted with glutamine transporters as well as glutaminase and inhibited their activation. The expression of mTOR, an apoptosis-related protein and downstream target of glutamine metabolism, was also inhibited by baicalein treatment. Importantly, we next demonstrated the suppression of mTOR signaling and the induction of apoptosis by baicalein were achieved by regulating glutamine metabolism. Conclusion: Baicalein inhibited the mTOR signaling pathway and induced apoptosis by downregulating glutamine metabolism. The potential of baicalein to induce apoptosis in lung cancer cells by selectively targeting the glutamine-mTOR pathway suggests an encouraging approach for treating lung cancer.http://www.sciencedirect.com/science/article/pii/S2090123224000857BaicaleinNon-small-cell lung cancerApoptosisMetabonomicsGlutamine-mTOR metabolic pathway |
| spellingShingle | Jingyang Li Di Zhang Shaohui Wang Peng Yu Jiayi Sun Yi Zhang Xianli Meng Juan Li Li Xiang Baicalein induces apoptosis by inhibiting the glutamine-mTOR metabolic pathway in lung cancer Journal of Advanced Research Baicalein Non-small-cell lung cancer Apoptosis Metabonomics Glutamine-mTOR metabolic pathway |
| title | Baicalein induces apoptosis by inhibiting the glutamine-mTOR metabolic pathway in lung cancer |
| title_full | Baicalein induces apoptosis by inhibiting the glutamine-mTOR metabolic pathway in lung cancer |
| title_fullStr | Baicalein induces apoptosis by inhibiting the glutamine-mTOR metabolic pathway in lung cancer |
| title_full_unstemmed | Baicalein induces apoptosis by inhibiting the glutamine-mTOR metabolic pathway in lung cancer |
| title_short | Baicalein induces apoptosis by inhibiting the glutamine-mTOR metabolic pathway in lung cancer |
| title_sort | baicalein induces apoptosis by inhibiting the glutamine mtor metabolic pathway in lung cancer |
| topic | Baicalein Non-small-cell lung cancer Apoptosis Metabonomics Glutamine-mTOR metabolic pathway |
| url | http://www.sciencedirect.com/science/article/pii/S2090123224000857 |
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