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Structure Elucidation and Anti-Tumor Activities of Trichothecenes from Endophytic Fungus Fusarium sporotrichioides

The secondary metabolites of Fusarium sporotrichioides, an endophytic fungus with anti-tumor activity isolated from Rauvolfia yunnanensis Tsiang, were investigated. Five trichothecenes, including one previously undescribed metabolite, were isolated and identified. Their structures were elucidated by...

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Autores principales: Wang, Ya-Jing, Ma, Nan, Lu, Yong-Fu, Dai, Si-Yang, Song, Xue, Li, Chang, Sun, Yi, Pei, Yue-Hu
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9220965/
https://www.ncbi.nlm.nih.gov/pubmed/35740903
http://dx.doi.org/10.3390/biom12060778
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author Wang, Ya-Jing
Ma, Nan
Lu, Yong-Fu
Dai, Si-Yang
Song, Xue
Li, Chang
Sun, Yi
Pei, Yue-Hu
author_facet Wang, Ya-Jing
Ma, Nan
Lu, Yong-Fu
Dai, Si-Yang
Song, Xue
Li, Chang
Sun, Yi
Pei, Yue-Hu
author_sort Wang, Ya-Jing
collection PubMed
description The secondary metabolites of Fusarium sporotrichioides, an endophytic fungus with anti-tumor activity isolated from Rauvolfia yunnanensis Tsiang, were investigated. Five trichothecenes, including one previously undescribed metabolite, were isolated and identified. Their structures were elucidated by means of extensive spectroscopic methods; the absolute configuration of compound 1 was determined by the ECD method. Surprisingly, 8-n-butyrylneosolaniol (3) exhibited stronger anti-tumor activity than T-2 toxin against Huh-7 cell line, with an IC(50) value of 265.9 nM. 8-n-butyrylneosolaniol (3) promoted apoptosis induction in Huh-7 cells. Moreover, cell cycle analysis showed that cell cycle arrest caused by 8-n-butyrylneosolaniol (3) at the G2/M phase resulted in cell proliferation inhibition and pro-apoptotic activity. Further studies showed a significant decrease in mitochondrial membrane permeabilization and a significant increase in ROS generation, which led to the activation of caspase cascades and subsequent cleavage of PARP fragments. In conclusion, 8-n-butyrylneosolaniol (3) induced cell apoptosis in Huh-7 cells via the mitochondria-mediated apoptotic signaling pathway, which could be a leading compound for anti-tumor agents.
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spelling pubmed-92209652022-06-24 Structure Elucidation and Anti-Tumor Activities of Trichothecenes from Endophytic Fungus Fusarium sporotrichioides Wang, Ya-Jing Ma, Nan Lu, Yong-Fu Dai, Si-Yang Song, Xue Li, Chang Sun, Yi Pei, Yue-Hu Biomolecules Article The secondary metabolites of Fusarium sporotrichioides, an endophytic fungus with anti-tumor activity isolated from Rauvolfia yunnanensis Tsiang, were investigated. Five trichothecenes, including one previously undescribed metabolite, were isolated and identified. Their structures were elucidated by means of extensive spectroscopic methods; the absolute configuration of compound 1 was determined by the ECD method. Surprisingly, 8-n-butyrylneosolaniol (3) exhibited stronger anti-tumor activity than T-2 toxin against Huh-7 cell line, with an IC(50) value of 265.9 nM. 8-n-butyrylneosolaniol (3) promoted apoptosis induction in Huh-7 cells. Moreover, cell cycle analysis showed that cell cycle arrest caused by 8-n-butyrylneosolaniol (3) at the G2/M phase resulted in cell proliferation inhibition and pro-apoptotic activity. Further studies showed a significant decrease in mitochondrial membrane permeabilization and a significant increase in ROS generation, which led to the activation of caspase cascades and subsequent cleavage of PARP fragments. In conclusion, 8-n-butyrylneosolaniol (3) induced cell apoptosis in Huh-7 cells via the mitochondria-mediated apoptotic signaling pathway, which could be a leading compound for anti-tumor agents. MDPI 2022-06-02 /pmc/articles/PMC9220965/ /pubmed/35740903 http://dx.doi.org/10.3390/biom12060778 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Wang, Ya-Jing
Ma, Nan
Lu, Yong-Fu
Dai, Si-Yang
Song, Xue
Li, Chang
Sun, Yi
Pei, Yue-Hu
Structure Elucidation and Anti-Tumor Activities of Trichothecenes from Endophytic Fungus Fusarium sporotrichioides
title Structure Elucidation and Anti-Tumor Activities of Trichothecenes from Endophytic Fungus Fusarium sporotrichioides
title_full Structure Elucidation and Anti-Tumor Activities of Trichothecenes from Endophytic Fungus Fusarium sporotrichioides
title_fullStr Structure Elucidation and Anti-Tumor Activities of Trichothecenes from Endophytic Fungus Fusarium sporotrichioides
title_full_unstemmed Structure Elucidation and Anti-Tumor Activities of Trichothecenes from Endophytic Fungus Fusarium sporotrichioides
title_short Structure Elucidation and Anti-Tumor Activities of Trichothecenes from Endophytic Fungus Fusarium sporotrichioides
title_sort structure elucidation and anti-tumor activities of trichothecenes from endophytic fungus fusarium sporotrichioides
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9220965/
https://www.ncbi.nlm.nih.gov/pubmed/35740903
http://dx.doi.org/10.3390/biom12060778
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