The ethyl acetate extract from Trichoderma viride fermentation acts by downregulating the leukocyte transendothelial migration signaling pathway to induce ferroptosis in triple-negative breast cancer cells

doi:10.1007/s13659-025-00569-w

Natural Products and Bioprospecting ›› 2026, Vol. 16 ›› Issue (1): 15-15.DOI: 10.1007/s13659-025-00569-w

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The ethyl acetate extract from Trichoderma viride fermentation acts by downregulating the leukocyte transendothelial migration signaling pathway to induce ferroptosis in triple-negative breast cancer cells

Yu Kuang¹, Bai-Hui Lu¹, Jia-Yi Wu¹, Song-Yu Wu¹, Hai-Yan Fu¹, Qing-Yan Nan³, Jing Li¹, Xiao-Long Yang^1,2

1. School of Pharmaceutical Sciences, South-Central Minzu University, Wuhan 430074, China;
2. School of Pharmacy, Anhui University of Chinese Medicine, Hefei 230012, China;
3. College of Life Sciences, South-Central Minzu University, Wuhan 430074, China

Received:2025-08-27 Online:2026-03-25 Published:2026-02-14
Contact: Jing Li,E-mail:jinglisxu@163.com;Xiao-Long Yang,E-mail:yxl19830915@163.com
Supported by:
This work was supported by the National Natural Science Foundation of China (grant number 82404451, 82473805); the Fundamental Research Funds for the Central Universities of South-Central Minzu University (grant number CZQ24025, CZH25030, YZY25002); the National Key R&D Program of China (grant number 2023YFF1104001) and Supported by the Fund for Academic Innovation Teams of South-Central Minzu University (Grant Number: XTZ24029).

The ethyl acetate extract from Trichoderma viride fermentation acts by downregulating the leukocyte transendothelial migration signaling pathway to induce ferroptosis in triple-negative breast cancer cells

Yu Kuang¹, Bai-Hui Lu¹, Jia-Yi Wu¹, Song-Yu Wu¹, Hai-Yan Fu¹, Qing-Yan Nan³, Jing Li¹, Xiao-Long Yang^1,2

1. School of Pharmaceutical Sciences, South-Central Minzu University, Wuhan 430074, China;
2. School of Pharmacy, Anhui University of Chinese Medicine, Hefei 230012, China;
3. College of Life Sciences, South-Central Minzu University, Wuhan 430074, China

通讯作者: Jing Li,E-mail:jinglisxu@163.com;Xiao-Long Yang,E-mail:yxl19830915@163.com
基金资助:
This work was supported by the National Natural Science Foundation of China (grant number 82404451, 82473805); the Fundamental Research Funds for the Central Universities of South-Central Minzu University (grant number CZQ24025, CZH25030, YZY25002); the National Key R&D Program of China (grant number 2023YFF1104001) and Supported by the Fund for Academic Innovation Teams of South-Central Minzu University (Grant Number: XTZ24029).

Abstract

Abstract: PurposeTriple-negative breast cancer (TNBC), characterized by the absence of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) expression, remains clinically challenging due to the lack of effective targeted therapies. This investigation revealed the anti-TNBC potential of Trichoderma viride ethyl acetate extract (TVEAE) from the endophytic fungus Trichoderma viride isolated from Coreopsis basalis.
MethodsPharmacological validation of TVEAE's anti-TNBC efficacy was conducted through in vitro and in vivo pharmacological models. The cell death mechanisms were systematically investigated using Hoechst staining, reactive oxygen species (ROS) detection, and lipid peroxidation assays. Potential therapeutic targets and signaling pathways were identified by integrating network pharmacology, transcriptomics, and weighted gene co-expression network analysis (WGCNA). Furthermore, this study validated key tumor-related proteins involved in tumor progression and cell death pathways via Western blotting. Finally, chemical constituents were characterized through molecular network coupled with Global Natural Products Social Molecular Networking (GNPS) analysis.
ResultsBoth in vitro and in vivo models established TVEAE's significant anti-TNBC efficacy. Mechanistic interrogation established TVEAE-mediated ferroptosis induction via selective modulation of leukocyte transendothelial migration (TEM) signaling cascades. Integrative analysis combining transcriptomics, WGCNA, and network pharmacology identified IL-6/TNF-α/HSP90AA1 as core therapeutic targets regulating TEM pathway dynamics. GNPS-assisted molecular networking uncovered six structurally novel anti-TNBC metabolites, including N-lauryldiethanolamine, erucamide, and Gliotoxin.
ConclusionThis study provides the first evidence of TVEAE's anti-TNBC activity through multi-target engagement along the leukocyte TEM signaling axis, effectively triggering ferroptosis. The mechanistic elucidation advances TNBC therapeutic development, offering a multi-dimensional targeting strategy against this recalcitrant malignancy.

Key words: Trichoderma viride, Triple-negative breast cancer, Leukocyte transendothelial migration, Ferroptosis

摘要： PurposeTriple-negative breast cancer (TNBC), characterized by the absence of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) expression, remains clinically challenging due to the lack of effective targeted therapies. This investigation revealed the anti-TNBC potential of Trichoderma viride ethyl acetate extract (TVEAE) from the endophytic fungus Trichoderma viride isolated from Coreopsis basalis.
MethodsPharmacological validation of TVEAE's anti-TNBC efficacy was conducted through in vitro and in vivo pharmacological models. The cell death mechanisms were systematically investigated using Hoechst staining, reactive oxygen species (ROS) detection, and lipid peroxidation assays. Potential therapeutic targets and signaling pathways were identified by integrating network pharmacology, transcriptomics, and weighted gene co-expression network analysis (WGCNA). Furthermore, this study validated key tumor-related proteins involved in tumor progression and cell death pathways via Western blotting. Finally, chemical constituents were characterized through molecular network coupled with Global Natural Products Social Molecular Networking (GNPS) analysis.
ResultsBoth in vitro and in vivo models established TVEAE's significant anti-TNBC efficacy. Mechanistic interrogation established TVEAE-mediated ferroptosis induction via selective modulation of leukocyte transendothelial migration (TEM) signaling cascades. Integrative analysis combining transcriptomics, WGCNA, and network pharmacology identified IL-6/TNF-α/HSP90AA1 as core therapeutic targets regulating TEM pathway dynamics. GNPS-assisted molecular networking uncovered six structurally novel anti-TNBC metabolites, including N-lauryldiethanolamine, erucamide, and Gliotoxin.
ConclusionThis study provides the first evidence of TVEAE's anti-TNBC activity through multi-target engagement along the leukocyte TEM signaling axis, effectively triggering ferroptosis. The mechanistic elucidation advances TNBC therapeutic development, offering a multi-dimensional targeting strategy against this recalcitrant malignancy.

关键词: Trichoderma viride, Triple-negative breast cancer, Leukocyte transendothelial migration, Ferroptosis

Yu Kuang, Bai-Hui Lu, Jia-Yi Wu, Song-Yu Wu, Hai-Yan Fu, Qing-Yan Nan, Jing Li, Xiao-Long Yang. The ethyl acetate extract from Trichoderma viride fermentation acts by downregulating the leukocyte transendothelial migration signaling pathway to induce ferroptosis in triple-negative breast cancer cells[J]. Natural Products and Bioprospecting, 2026, 16(1): 15-15.

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The ethyl acetate extract from Trichoderma viride fermentation acts by downregulating the leukocyte transendothelial migration signaling pathway to induce ferroptosis in triple-negative breast cancer cells

The ethyl acetate extract from Trichoderma viride fermentation acts by downregulating the leukocyte transendothelial migration signaling pathway to induce ferroptosis in triple-negative breast cancer cells

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