In vitro Non-Small Cell Lung Cancer Inhibitory Effect by New Diphenylethane Isolated From Stems and Leaves of Dioscorea oppositifolia L. via ERβ-STAT3 Pathway
Lung cancer is the most leading cause of cancer mortality throughout the world, of which about 85% cases comprise the non-small cell lung cancer (NSCLC). Estrogen and estrogen receptors are known to be involved in the pathogenesis and development of lung cancer. Dioscorea oppositifolia L. is a tradi...
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Frontiers Media S.A.
2021-02-01
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| Series: | Frontiers in Pharmacology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fphar.2021.622681/full |
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| author | Mengnan Zeng Mengnan Zeng Mengnan Zeng Yingjie Ren Yingjie Ren Beibei Zhang Beibei Zhang Shengchao Wang Shengchao Wang Meng Liu Meng Liu Jufang Jia Jufang Jia Pengli Guo Pengli Guo Qinqin Zhang Qinqin Zhang Xiaoke Zheng Xiaoke Zheng Xiaoke Zheng Weisheng Feng Weisheng Feng Weisheng Feng |
| author_facet | Mengnan Zeng Mengnan Zeng Mengnan Zeng Yingjie Ren Yingjie Ren Beibei Zhang Beibei Zhang Shengchao Wang Shengchao Wang Meng Liu Meng Liu Jufang Jia Jufang Jia Pengli Guo Pengli Guo Qinqin Zhang Qinqin Zhang Xiaoke Zheng Xiaoke Zheng Xiaoke Zheng Weisheng Feng Weisheng Feng Weisheng Feng |
| author_sort | Mengnan Zeng |
| collection | DOAJ |
| description | Lung cancer is the most leading cause of cancer mortality throughout the world, of which about 85% cases comprise the non-small cell lung cancer (NSCLC). Estrogen and estrogen receptors are known to be involved in the pathogenesis and development of lung cancer. Dioscorea oppositifolia L. is a traditional Chinese medicine and a nutritious food, and can be an excellent candidate as an anti-cancer agent owing to its estrogen-like effects. However, the stems and leaves of D. oppositifolia L. are piled up in the field as a waste, causing environmental pollution and waste of resources. In the present study, a new diphenylethane (D1) was isolated from the stems and leaves of D. oppositifolia L. It was observed that D1 reduced the cell viability, migration, energy metabolism, and induced apoptosis in the A549 cells. Mechanistic studies showed that D1 reduced the STAT3 nuclear localization and downregulated the expression of the STAT3 target genes like Mcl-1, Bcl-xL and MMP-2 that are involved in the cell survival and mobility. Moreover, our results indicated that D1 exhibited estrogenic activities mediated by ERβ, and antagonising ERβ decreased the cytotoxic effect of D1 in A549 cells. In addition, inhibition of the nuclear translocation of STAT3 did not interfere with the binding of D1 and ERβ. However, after antagonizing ERβ, the nuclear translocation of STAT3 increased, thereby demonstrating that STAT3 was the downstream signaling molecule of ERβ. In conclusion, the D1 mediated anti-NSCLC in vitro effects or at least in part can be attributed to the ERβ-STAT3 signaling. Our findings suggest the role of D1 in treating NSCLC on a molecular level, and can help to improve the comprehensive utilization rate of D. oppositifolia L. |
| first_indexed | 2024-12-14T10:03:07Z |
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| id | doaj.art-3571afdecd3c4c4eb9de01ed2c5ced2a |
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| language | English |
| last_indexed | 2024-12-14T10:03:07Z |
| publishDate | 2021-02-01 |
| publisher | Frontiers Media S.A. |
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| series | Frontiers in Pharmacology |
| spelling | doaj.art-3571afdecd3c4c4eb9de01ed2c5ced2a2022-12-21T23:07:13ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122021-02-011210.3389/fphar.2021.622681622681In vitro Non-Small Cell Lung Cancer Inhibitory Effect by New Diphenylethane Isolated From Stems and Leaves of Dioscorea oppositifolia L. via ERβ-STAT3 PathwayMengnan Zeng0Mengnan Zeng1Mengnan Zeng2Yingjie Ren3Yingjie Ren4Beibei Zhang5Beibei Zhang6Shengchao Wang7Shengchao Wang8Meng Liu9Meng Liu10Jufang Jia11Jufang Jia12Pengli Guo13Pengli Guo14Qinqin Zhang15Qinqin Zhang16Xiaoke Zheng17Xiaoke Zheng18Xiaoke Zheng19Weisheng Feng20Weisheng Feng21Weisheng Feng22College of Pharmacy, Henan University of Chinese Medicine, Zhengzhou, ChinaThe Engineering and Technology Center for Chinese Medicine Development of Henan Province, Zhengzhou, ChinaHenan University of Chinese Medicine, Co-construction of Collaborative Innovation Center for Chinese Medicine and Respiratory Diseases by Henan & Education Ministry of P.R. China, Zhengzhou, ChinaCollege of Pharmacy, Henan University of Chinese Medicine, Zhengzhou, ChinaThe Engineering and Technology Center for Chinese Medicine Development of Henan Province, Zhengzhou, ChinaCollege of Pharmacy, Henan University of Chinese Medicine, Zhengzhou, ChinaThe Engineering and Technology Center for Chinese Medicine Development of Henan Province, Zhengzhou, ChinaCollege of Pharmacy, Henan University of Chinese Medicine, Zhengzhou, ChinaThe Engineering and Technology Center for Chinese Medicine Development of Henan Province, Zhengzhou, ChinaCollege of Pharmacy, Henan University of Chinese Medicine, Zhengzhou, ChinaThe Engineering and Technology Center for Chinese Medicine Development of Henan Province, Zhengzhou, ChinaCollege of Pharmacy, Henan University of Chinese Medicine, Zhengzhou, ChinaThe Engineering and Technology Center for Chinese Medicine Development of Henan Province, Zhengzhou, ChinaCollege of Pharmacy, Henan University of Chinese Medicine, Zhengzhou, ChinaThe Engineering and Technology Center for Chinese Medicine Development of Henan Province, Zhengzhou, ChinaCollege of Pharmacy, Henan University of Chinese Medicine, Zhengzhou, ChinaThe Engineering and Technology Center for Chinese Medicine Development of Henan Province, Zhengzhou, ChinaCollege of Pharmacy, Henan University of Chinese Medicine, Zhengzhou, ChinaThe Engineering and Technology Center for Chinese Medicine Development of Henan Province, Zhengzhou, ChinaHenan University of Chinese Medicine, Co-construction of Collaborative Innovation Center for Chinese Medicine and Respiratory Diseases by Henan & Education Ministry of P.R. China, Zhengzhou, ChinaCollege of Pharmacy, Henan University of Chinese Medicine, Zhengzhou, ChinaThe Engineering and Technology Center for Chinese Medicine Development of Henan Province, Zhengzhou, ChinaHenan University of Chinese Medicine, Co-construction of Collaborative Innovation Center for Chinese Medicine and Respiratory Diseases by Henan & Education Ministry of P.R. China, Zhengzhou, ChinaLung cancer is the most leading cause of cancer mortality throughout the world, of which about 85% cases comprise the non-small cell lung cancer (NSCLC). Estrogen and estrogen receptors are known to be involved in the pathogenesis and development of lung cancer. Dioscorea oppositifolia L. is a traditional Chinese medicine and a nutritious food, and can be an excellent candidate as an anti-cancer agent owing to its estrogen-like effects. However, the stems and leaves of D. oppositifolia L. are piled up in the field as a waste, causing environmental pollution and waste of resources. In the present study, a new diphenylethane (D1) was isolated from the stems and leaves of D. oppositifolia L. It was observed that D1 reduced the cell viability, migration, energy metabolism, and induced apoptosis in the A549 cells. Mechanistic studies showed that D1 reduced the STAT3 nuclear localization and downregulated the expression of the STAT3 target genes like Mcl-1, Bcl-xL and MMP-2 that are involved in the cell survival and mobility. Moreover, our results indicated that D1 exhibited estrogenic activities mediated by ERβ, and antagonising ERβ decreased the cytotoxic effect of D1 in A549 cells. In addition, inhibition of the nuclear translocation of STAT3 did not interfere with the binding of D1 and ERβ. However, after antagonizing ERβ, the nuclear translocation of STAT3 increased, thereby demonstrating that STAT3 was the downstream signaling molecule of ERβ. In conclusion, the D1 mediated anti-NSCLC in vitro effects or at least in part can be attributed to the ERβ-STAT3 signaling. Our findings suggest the role of D1 in treating NSCLC on a molecular level, and can help to improve the comprehensive utilization rate of D. oppositifolia L.https://www.frontiersin.org/articles/10.3389/fphar.2021.622681/fullnew diphenylethanenon-small cell lung cancerERβstat3stems and leaves of Dioscorea oppositifolia L |
| spellingShingle | Mengnan Zeng Mengnan Zeng Mengnan Zeng Yingjie Ren Yingjie Ren Beibei Zhang Beibei Zhang Shengchao Wang Shengchao Wang Meng Liu Meng Liu Jufang Jia Jufang Jia Pengli Guo Pengli Guo Qinqin Zhang Qinqin Zhang Xiaoke Zheng Xiaoke Zheng Xiaoke Zheng Weisheng Feng Weisheng Feng Weisheng Feng In vitro Non-Small Cell Lung Cancer Inhibitory Effect by New Diphenylethane Isolated From Stems and Leaves of Dioscorea oppositifolia L. via ERβ-STAT3 Pathway Frontiers in Pharmacology new diphenylethane non-small cell lung cancer ERβ stat3 stems and leaves of Dioscorea oppositifolia L |
| title | In vitro Non-Small Cell Lung Cancer Inhibitory Effect by New Diphenylethane Isolated From Stems and Leaves of Dioscorea oppositifolia L. via ERβ-STAT3 Pathway |
| title_full | In vitro Non-Small Cell Lung Cancer Inhibitory Effect by New Diphenylethane Isolated From Stems and Leaves of Dioscorea oppositifolia L. via ERβ-STAT3 Pathway |
| title_fullStr | In vitro Non-Small Cell Lung Cancer Inhibitory Effect by New Diphenylethane Isolated From Stems and Leaves of Dioscorea oppositifolia L. via ERβ-STAT3 Pathway |
| title_full_unstemmed | In vitro Non-Small Cell Lung Cancer Inhibitory Effect by New Diphenylethane Isolated From Stems and Leaves of Dioscorea oppositifolia L. via ERβ-STAT3 Pathway |
| title_short | In vitro Non-Small Cell Lung Cancer Inhibitory Effect by New Diphenylethane Isolated From Stems and Leaves of Dioscorea oppositifolia L. via ERβ-STAT3 Pathway |
| title_sort | in vitro non small cell lung cancer inhibitory effect by new diphenylethane isolated from stems and leaves of dioscorea oppositifolia l via erβ stat3 pathway |
| topic | new diphenylethane non-small cell lung cancer ERβ stat3 stems and leaves of Dioscorea oppositifolia L |
| url | https://www.frontiersin.org/articles/10.3389/fphar.2021.622681/full |
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