Dauricine Impedes the Tumorigenesis of Lung Adenocarcinoma by Regulating Nrf2 and Reactive Oxygen Species
Dauricine has been shown to possess intriguing anti-cancerous activities against various malignancies. The current study examined the inhibitory effects of dauricine against lung adenocarcinoma with cell lines and animal models. MTT assay was performed in three different lung adenocarcinoma cell lin...
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2025-05-01
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| author | Waleed Yousuf Nimra Zafar Siddiqui Perbhat Ali Shaoxuan Cheng Immad Ansari Jialiang Song Minghe Dai Zhiyuan Qiu Yue Zhu Yaowen Zhang Shuyan Liu Yingqiu Zhang Zhenhua Liu Han Liu |
| author_facet | Waleed Yousuf Nimra Zafar Siddiqui Perbhat Ali Shaoxuan Cheng Immad Ansari Jialiang Song Minghe Dai Zhiyuan Qiu Yue Zhu Yaowen Zhang Shuyan Liu Yingqiu Zhang Zhenhua Liu Han Liu |
| author_sort | Waleed Yousuf |
| collection | DOAJ |
| description | Dauricine has been shown to possess intriguing anti-cancerous activities against various malignancies. The current study examined the inhibitory effects of dauricine against lung adenocarcinoma with cell lines and animal models. MTT assay was performed in three different lung adenocarcinoma cell lines using a concentration range of dauricine. Colony formation, wound healing, Edu incorporation, and cell cycle analysis were conducted to investigate the impact of dauricine on lung adenocarcinoma cells in vitro. Moreover, flow cytometry was performed to observe the effect of dauricine on cellular ROS levels. The expression of redox regulator Nrf2 and apoptosis-related markers was assessed by Western blot. Importantly, the anti-tumor efficacy of dauricine was studied in vivo with two lung adenocarcinoma animal models, including a subcutaneous cell line-derived syngeneic model and an inducible orthotopic <i>KRAS<sup>G12D</sup></i>-driven lung adenocarcinoma model. The proliferation and migration of lung adenocarcinoma cells were significantly reduced by dauricine treatment. Flow cytometry analysis revealed that dauricine treatment resulted in cell cycle arrest at G0/G1 phases in A549, H1299, and A427 cells. Intracellular ROS levels were markedly augmented by dauricine treatment. Notably, dauricine led to the downregulation of the master redox regulator Nrf2. Meanwhile, dauricine treatment resulted in decreased Bcl-2 levels but elevated expression of BAX and cleaved Caspase 3. Finally, dauricine demonstrated significant efficacy in restricting tumor progression in both subcutaneous syngeneic and orthotopic lung adenocarcinoma models. Our results corroborate the anti-cancer effects of dauricine against lung adenocarcinoma with in vivo and in vitro analyses. Our findings also provide mechanistic evidence that links the impact of dauricine to cell cycle blockage and ROS-mediated apoptosis. |
| format | Article |
| id | doaj-art-cf1bc92643da4273965c3158cf6f3cee |
| institution | OA Journals |
| issn | 2073-4409 |
| language | English |
| publishDate | 2025-05-01 |
| publisher | MDPI AG |
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| series | Cells |
| spelling | doaj-art-cf1bc92643da4273965c3158cf6f3cee2025-08-20T02:33:38ZengMDPI AGCells2073-44092025-05-01141069810.3390/cells14100698Dauricine Impedes the Tumorigenesis of Lung Adenocarcinoma by Regulating Nrf2 and Reactive Oxygen SpeciesWaleed Yousuf0Nimra Zafar Siddiqui1Perbhat Ali2Shaoxuan Cheng3Immad Ansari4Jialiang Song5Minghe Dai6Zhiyuan Qiu7Yue Zhu8Yaowen Zhang9Shuyan Liu10Yingqiu Zhang11Zhenhua Liu12Han Liu13Institute of Cancer Stem Cell, Dalian Medical University, Dalian 116044, ChinaInstitute of Cancer Stem Cell, Dalian Medical University, Dalian 116044, ChinaInstitute of Cancer Stem Cell, Dalian Medical University, Dalian 116044, ChinaInstitute of Cancer Stem Cell, Dalian Medical University, Dalian 116044, ChinaSchool of Basic Medical Sciences, Dalian Medical University, Dalian 116044, ChinaInstitute of Cancer Stem Cell, Dalian Medical University, Dalian 116044, ChinaInstitute of Cancer Stem Cell, Dalian Medical University, Dalian 116044, ChinaInstitute of Cancer Stem Cell, Dalian Medical University, Dalian 116044, ChinaInstitute of Cancer Stem Cell, Dalian Medical University, Dalian 116044, ChinaInstitute of Cancer Stem Cell, Dalian Medical University, Dalian 116044, ChinaInstitute of Cancer Stem Cell, Dalian Medical University, Dalian 116044, ChinaInstitute of Cancer Stem Cell, Dalian Medical University, Dalian 116044, ChinaInstitute of Cancer Stem Cell, Dalian Medical University, Dalian 116044, ChinaInstitute of Cancer Stem Cell, Dalian Medical University, Dalian 116044, ChinaDauricine has been shown to possess intriguing anti-cancerous activities against various malignancies. The current study examined the inhibitory effects of dauricine against lung adenocarcinoma with cell lines and animal models. MTT assay was performed in three different lung adenocarcinoma cell lines using a concentration range of dauricine. Colony formation, wound healing, Edu incorporation, and cell cycle analysis were conducted to investigate the impact of dauricine on lung adenocarcinoma cells in vitro. Moreover, flow cytometry was performed to observe the effect of dauricine on cellular ROS levels. The expression of redox regulator Nrf2 and apoptosis-related markers was assessed by Western blot. Importantly, the anti-tumor efficacy of dauricine was studied in vivo with two lung adenocarcinoma animal models, including a subcutaneous cell line-derived syngeneic model and an inducible orthotopic <i>KRAS<sup>G12D</sup></i>-driven lung adenocarcinoma model. The proliferation and migration of lung adenocarcinoma cells were significantly reduced by dauricine treatment. Flow cytometry analysis revealed that dauricine treatment resulted in cell cycle arrest at G0/G1 phases in A549, H1299, and A427 cells. Intracellular ROS levels were markedly augmented by dauricine treatment. Notably, dauricine led to the downregulation of the master redox regulator Nrf2. Meanwhile, dauricine treatment resulted in decreased Bcl-2 levels but elevated expression of BAX and cleaved Caspase 3. Finally, dauricine demonstrated significant efficacy in restricting tumor progression in both subcutaneous syngeneic and orthotopic lung adenocarcinoma models. Our results corroborate the anti-cancer effects of dauricine against lung adenocarcinoma with in vivo and in vitro analyses. Our findings also provide mechanistic evidence that links the impact of dauricine to cell cycle blockage and ROS-mediated apoptosis.https://www.mdpi.com/2073-4409/14/10/698dauricinelung adenocarcinoma (LUAD)cell growthcell migrationapoptosisROS |
| spellingShingle | Waleed Yousuf Nimra Zafar Siddiqui Perbhat Ali Shaoxuan Cheng Immad Ansari Jialiang Song Minghe Dai Zhiyuan Qiu Yue Zhu Yaowen Zhang Shuyan Liu Yingqiu Zhang Zhenhua Liu Han Liu Dauricine Impedes the Tumorigenesis of Lung Adenocarcinoma by Regulating Nrf2 and Reactive Oxygen Species Cells dauricine lung adenocarcinoma (LUAD) cell growth cell migration apoptosis ROS |
| title | Dauricine Impedes the Tumorigenesis of Lung Adenocarcinoma by Regulating Nrf2 and Reactive Oxygen Species |
| title_full | Dauricine Impedes the Tumorigenesis of Lung Adenocarcinoma by Regulating Nrf2 and Reactive Oxygen Species |
| title_fullStr | Dauricine Impedes the Tumorigenesis of Lung Adenocarcinoma by Regulating Nrf2 and Reactive Oxygen Species |
| title_full_unstemmed | Dauricine Impedes the Tumorigenesis of Lung Adenocarcinoma by Regulating Nrf2 and Reactive Oxygen Species |
| title_short | Dauricine Impedes the Tumorigenesis of Lung Adenocarcinoma by Regulating Nrf2 and Reactive Oxygen Species |
| title_sort | dauricine impedes the tumorigenesis of lung adenocarcinoma by regulating nrf2 and reactive oxygen species |
| topic | dauricine lung adenocarcinoma (LUAD) cell growth cell migration apoptosis ROS |
| url | https://www.mdpi.com/2073-4409/14/10/698 |
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