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Understanding of cell death induced by the constituents of Taxus yunnanensis wood

The ethanol extract from the wood of Taxus Yunnanensis (TY) induced apoptosis in all cancer cell lines tested, which was mainly due to activation of an extrinsic pathway in human colon cancer DLD-1 cells. The extrinsic pathway was activated by the upregulation of the expression levels of Fas and TRA...

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Autores principales: Akao, Yukihiro, Terazawa, Riyako, Sugito, Nobuhiko, Heishima, Kazuki, Morikawa, Kohei, Ito, Yuko, Narui, Ryoko, Hamaguchi, Reo, Nobukawa, Takahiro
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9012736/
https://www.ncbi.nlm.nih.gov/pubmed/35428370
http://dx.doi.org/10.1038/s41598-022-09655-2
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author Akao, Yukihiro
Terazawa, Riyako
Sugito, Nobuhiko
Heishima, Kazuki
Morikawa, Kohei
Ito, Yuko
Narui, Ryoko
Hamaguchi, Reo
Nobukawa, Takahiro
author_facet Akao, Yukihiro
Terazawa, Riyako
Sugito, Nobuhiko
Heishima, Kazuki
Morikawa, Kohei
Ito, Yuko
Narui, Ryoko
Hamaguchi, Reo
Nobukawa, Takahiro
author_sort Akao, Yukihiro
collection PubMed
description The ethanol extract from the wood of Taxus Yunnanensis (TY) induced apoptosis in all cancer cell lines tested, which was mainly due to activation of an extrinsic pathway in human colon cancer DLD-1 cells. The extrinsic pathway was activated by the upregulation of the expression levels of Fas and TRAIL/DR5, which led to the activation of caspase-8. Of note, the machinery of this increase in expression was promoted by the upregulation of MIR32a expression, which silenced MIR34a-targeting E2F3 transcription factor. Furthermore, ectopic expression of MIR32a or siR-E2F3 silencing E2F3 increased Fas and TRAIL/DR5 expression. Thus, the extract activated the extrinsic pathway through the MIR34a/E2F3 axis, resulting in the autocrine and paracrine release of TRAIL, and upregulated expression of death receptors Fas and DR5 in the treated DLD-1 cells, which were functionally validated by Fas immunocytochemistry, and using anti-Fas and anti-TRAIL antibodies, respectively. In vivo, TY showed significant anti-tumor effects on xenografted and syngeneic model mice. The extract may also aid in chemoprevention by selectively making marked tumor cells susceptible to the tumor immunosurveillance system.
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spelling pubmed-90127362022-04-18 Understanding of cell death induced by the constituents of Taxus yunnanensis wood Akao, Yukihiro Terazawa, Riyako Sugito, Nobuhiko Heishima, Kazuki Morikawa, Kohei Ito, Yuko Narui, Ryoko Hamaguchi, Reo Nobukawa, Takahiro Sci Rep Article The ethanol extract from the wood of Taxus Yunnanensis (TY) induced apoptosis in all cancer cell lines tested, which was mainly due to activation of an extrinsic pathway in human colon cancer DLD-1 cells. The extrinsic pathway was activated by the upregulation of the expression levels of Fas and TRAIL/DR5, which led to the activation of caspase-8. Of note, the machinery of this increase in expression was promoted by the upregulation of MIR32a expression, which silenced MIR34a-targeting E2F3 transcription factor. Furthermore, ectopic expression of MIR32a or siR-E2F3 silencing E2F3 increased Fas and TRAIL/DR5 expression. Thus, the extract activated the extrinsic pathway through the MIR34a/E2F3 axis, resulting in the autocrine and paracrine release of TRAIL, and upregulated expression of death receptors Fas and DR5 in the treated DLD-1 cells, which were functionally validated by Fas immunocytochemistry, and using anti-Fas and anti-TRAIL antibodies, respectively. In vivo, TY showed significant anti-tumor effects on xenografted and syngeneic model mice. The extract may also aid in chemoprevention by selectively making marked tumor cells susceptible to the tumor immunosurveillance system. Nature Publishing Group UK 2022-04-15 /pmc/articles/PMC9012736/ /pubmed/35428370 http://dx.doi.org/10.1038/s41598-022-09655-2 Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Akao, Yukihiro
Terazawa, Riyako
Sugito, Nobuhiko
Heishima, Kazuki
Morikawa, Kohei
Ito, Yuko
Narui, Ryoko
Hamaguchi, Reo
Nobukawa, Takahiro
Understanding of cell death induced by the constituents of Taxus yunnanensis wood
title Understanding of cell death induced by the constituents of Taxus yunnanensis wood
title_full Understanding of cell death induced by the constituents of Taxus yunnanensis wood
title_fullStr Understanding of cell death induced by the constituents of Taxus yunnanensis wood
title_full_unstemmed Understanding of cell death induced by the constituents of Taxus yunnanensis wood
title_short Understanding of cell death induced by the constituents of Taxus yunnanensis wood
title_sort understanding of cell death induced by the constituents of taxus yunnanensis wood
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9012736/
https://www.ncbi.nlm.nih.gov/pubmed/35428370
http://dx.doi.org/10.1038/s41598-022-09655-2
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