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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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Autores principales: Zeng, Mengnan, Ren, Yingjie, Zhang, Beibei, Wang, Shengchao, Liu, Meng, Jia, Jufang, Guo, Pengli, Zhang, Qinqin, Zheng, Xiaoke, Feng, Weisheng
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7941213/
https://www.ncbi.nlm.nih.gov/pubmed/33708130
http://dx.doi.org/10.3389/fphar.2021.622681
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author Zeng, Mengnan
Ren, Yingjie
Zhang, Beibei
Wang, Shengchao
Liu, Meng
Jia, Jufang
Guo, Pengli
Zhang, Qinqin
Zheng, Xiaoke
Feng, Weisheng
author_facet Zeng, Mengnan
Ren, Yingjie
Zhang, Beibei
Wang, Shengchao
Liu, Meng
Jia, Jufang
Guo, Pengli
Zhang, Qinqin
Zheng, Xiaoke
Feng, Weisheng
author_sort Zeng, Mengnan
collection PubMed
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.
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spelling pubmed-79412132021-03-10 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 Zeng, Mengnan Ren, Yingjie Zhang, Beibei Wang, Shengchao Liu, Meng Jia, Jufang Guo, Pengli Zhang, Qinqin Zheng, Xiaoke Feng, Weisheng Front Pharmacol Pharmacology 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. Frontiers Media S.A. 2021-02-02 /pmc/articles/PMC7941213/ /pubmed/33708130 http://dx.doi.org/10.3389/fphar.2021.622681 Text en Copyright © 2021 Zeng, Ren, Zhang, Wang, Liu, Jia, Guo, Zhang, Zheng and Feng. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY) (http://creativecommons.org/licenses/by/4.0/) . The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Pharmacology
Zeng, Mengnan
Ren, Yingjie
Zhang, Beibei
Wang, Shengchao
Liu, Meng
Jia, Jufang
Guo, Pengli
Zhang, Qinqin
Zheng, Xiaoke
Feng, Weisheng
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 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 Pharmacology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7941213/
https://www.ncbi.nlm.nih.gov/pubmed/33708130
http://dx.doi.org/10.3389/fphar.2021.622681
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