A Meroterpenoid from Tibetan Medicine Induces Lung Cancer Cells Apoptosis through ROS-Mediated Inactivation of the AKT Pathway
As a traditional Tibetan medicine in China, <i>Meconopsis grandis</i> Prain has been used to treat a variety of illnesses by local people for thousands of years. However, the active ingredients contained in <i>Meconopsis grandis</i> Prain and its pharmacodynamic mechanisms ha...
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MDPI AG
2023-02-01
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| Series: | Molecules |
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| Online Access: | https://www.mdpi.com/1420-3049/28/4/1939 |
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| author | Yi Huang Yun Huang Ge Zhu Bingzhi Zhang Yujia Zhu Bin Chen Xiaoxia Gao Jie Yuan |
| author_facet | Yi Huang Yun Huang Ge Zhu Bingzhi Zhang Yujia Zhu Bin Chen Xiaoxia Gao Jie Yuan |
| author_sort | Yi Huang |
| collection | DOAJ |
| description | As a traditional Tibetan medicine in China, <i>Meconopsis grandis</i> Prain has been used to treat a variety of illnesses by local people for thousands of years. However, the active ingredients contained in <i>Meconopsis grandis</i> Prain and its pharmacodynamic mechanisms have scarcely been reported. We isolated a meroterpenoid named D1399 from <i>Meconopsis grandis</i> Prain endophytic fungi with strong antitumor activity. The structure analysis showed that D1399 is an alkaloid containing a 13-membered macrocyclic structure. The IC<sub>50</sub> of D1399 for human lung cancer cells’ viability ranged from 0.88 to 2.45 μM. Furthermore, we utilized TUNEL assay and western blotting to investigate the antitumor effectiveness of D1399. The results have shown that D1399 induced the apoptosis of lung cancer cells on the extrinsic and intrinsic pathways by boosting ROS generation and repressing AKT activity. In the mouse xenograft model, the average tumor weight with 30 mg·kg<sup>−1</sup> D1399 treatment exhibited 73.19% inhibition compared with the untreated control, without affecting body weight loss. Above all, for the first time, our study provides a possible mechanism for the antitumor activity of D1399 in vitro and in vivo as a natural product from Tibetan medicine with <i>Meconopsis grandis</i> Prain, which may be a potentially promising antitumor drug candidate. |
| first_indexed | 2024-03-11T08:21:08Z |
| format | Article |
| id | doaj.art-8d2976d366f844fb86c3e749b924d0ec |
| institution | Directory Open Access Journal |
| issn | 1420-3049 |
| language | English |
| last_indexed | 2024-03-11T08:21:08Z |
| publishDate | 2023-02-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Molecules |
| spelling | doaj.art-8d2976d366f844fb86c3e749b924d0ec2023-11-16T22:25:18ZengMDPI AGMolecules1420-30492023-02-01284193910.3390/molecules28041939A Meroterpenoid from Tibetan Medicine Induces Lung Cancer Cells Apoptosis through ROS-Mediated Inactivation of the AKT PathwayYi Huang0Yun Huang1Ge Zhu2Bingzhi Zhang3Yujia Zhu4Bin Chen5Xiaoxia Gao6Jie Yuan7Key Laboratory of Tropical Disease Control (Sun Yat-sen University), Ministry of Education, Guangzhou 510080, ChinaSchool of Basic Medical Sciences, Southern Medical University, Guangzhou 510515, ChinaDepartment of Biochemistry, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou 510080, ChinaSchool of Pharmacy, Guangdong Pharmaceutical University, Guangzhou 510006, ChinaSchool of Public Health, Sun Yat-sen University, Guangzhou 510080, ChinaSouthern Laboratory of Ocean Science and Engineering, Zhuhai 519000, ChinaSchool of Pharmacy, Guangdong Pharmaceutical University, Guangzhou 510006, ChinaKey Laboratory of Tropical Disease Control (Sun Yat-sen University), Ministry of Education, Guangzhou 510080, ChinaAs a traditional Tibetan medicine in China, <i>Meconopsis grandis</i> Prain has been used to treat a variety of illnesses by local people for thousands of years. However, the active ingredients contained in <i>Meconopsis grandis</i> Prain and its pharmacodynamic mechanisms have scarcely been reported. We isolated a meroterpenoid named D1399 from <i>Meconopsis grandis</i> Prain endophytic fungi with strong antitumor activity. The structure analysis showed that D1399 is an alkaloid containing a 13-membered macrocyclic structure. The IC<sub>50</sub> of D1399 for human lung cancer cells’ viability ranged from 0.88 to 2.45 μM. Furthermore, we utilized TUNEL assay and western blotting to investigate the antitumor effectiveness of D1399. The results have shown that D1399 induced the apoptosis of lung cancer cells on the extrinsic and intrinsic pathways by boosting ROS generation and repressing AKT activity. In the mouse xenograft model, the average tumor weight with 30 mg·kg<sup>−1</sup> D1399 treatment exhibited 73.19% inhibition compared with the untreated control, without affecting body weight loss. Above all, for the first time, our study provides a possible mechanism for the antitumor activity of D1399 in vitro and in vivo as a natural product from Tibetan medicine with <i>Meconopsis grandis</i> Prain, which may be a potentially promising antitumor drug candidate.https://www.mdpi.com/1420-3049/28/4/1939D1399meroterpenoidTibetan medicineapoptosisROSAKT |
| spellingShingle | Yi Huang Yun Huang Ge Zhu Bingzhi Zhang Yujia Zhu Bin Chen Xiaoxia Gao Jie Yuan A Meroterpenoid from Tibetan Medicine Induces Lung Cancer Cells Apoptosis through ROS-Mediated Inactivation of the AKT Pathway Molecules D1399 meroterpenoid Tibetan medicine apoptosis ROS AKT |
| title | A Meroterpenoid from Tibetan Medicine Induces Lung Cancer Cells Apoptosis through ROS-Mediated Inactivation of the AKT Pathway |
| title_full | A Meroterpenoid from Tibetan Medicine Induces Lung Cancer Cells Apoptosis through ROS-Mediated Inactivation of the AKT Pathway |
| title_fullStr | A Meroterpenoid from Tibetan Medicine Induces Lung Cancer Cells Apoptosis through ROS-Mediated Inactivation of the AKT Pathway |
| title_full_unstemmed | A Meroterpenoid from Tibetan Medicine Induces Lung Cancer Cells Apoptosis through ROS-Mediated Inactivation of the AKT Pathway |
| title_short | A Meroterpenoid from Tibetan Medicine Induces Lung Cancer Cells Apoptosis through ROS-Mediated Inactivation of the AKT Pathway |
| title_sort | meroterpenoid from tibetan medicine induces lung cancer cells apoptosis through ros mediated inactivation of the akt pathway |
| topic | D1399 meroterpenoid Tibetan medicine apoptosis ROS AKT |
| url | https://www.mdpi.com/1420-3049/28/4/1939 |
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