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ArticleCurrent medicinal chemistry2025

HTB50-2 Inhibits Growth and Migration of Triple-negative Breast Cancer via FOSL2/FOXC1 Signaling Axis and Subsequent Ferroptosis.

Na Liu, Wenying Yin, Wenqi Duan, Yuzhu Lyu, Shan Xie, Lei Fang, Yan Ji, Feng-Ying Yang, Di Ge

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Article in Current medicinal chemistry, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

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1citing papers in PubMed
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1 · What the graph read from it

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3 · Its place in the literature

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1 citing paper in PubMed.

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4 · The record

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5 · Who and what money

Authors and funding

9 authors.

Na LiuSchool of Biological Science and Technology, University of Jinan, Jinan, 250022, China.
Wenying YinSchool of Biological Science and Technology, University of Jinan, Jinan, 250022, China.
Wenqi DuanSchool of Biological Science and Technology, University of Jinan, Jinan, 250022, China.
Yuzhu LyuSchool of Biological Science and Technology, University of Jinan, Jinan, 250022, China.
Shan XieSchool of Biological Science and Technology, University of Jinan, Jinan, 250022, China.
Lei FangSchool of Biological Science and Technology, University of Jinan, Jinan, 250022, China.
Yan JiSchool of Biological Science and Technology, University of Jinan, Jinan, 250022, China.
Feng-Ying YangSchool of Biological Science and Technology, University of Jinan, Jinan, 250022, China.
Di GeSchool of Biological Science and Technology, University of Jinan, Jinan, 250022, China.

Funding

Doctor Fund of the University of Jinan XBS1520Higher Educational Science and Technology Program of Jinan City 2020GXRC060National Natural Science Foundation of China 82073728, 31501122Natural Science Foundation of Shandong Province ZR2021MH357, ZR2019QH006
6 · The paper itself

Abstract

backgroundThe manipulation of ferroptosis in cancer cells is a possible therapeutic technique that has been investigated for use in the treatment of cancer. Consequently, ferroptosis-inducing medications have recently received increased interest in cancer therapy. In this research, we assessed the anticancer efficacy of 14β-hydroxy- 3β-(β-D-Glucopyranosyloxy)-5α-bufa-20,22-dienolide (HTB50-2), a natural product derived from the plant Helleborus thibetanus Franch, in Triple-Negative Breast Cancer (TNBC). Moreover, we also studied its potential mechanisms.

methodsThe biological effects of HTB50-2 in a series of breast cancer cell lines were analyzed using sulforhodamine B (SRB) and other methods. The migration ability was analyzed using three methods: wound healing assay, transwell assay, and Western blot. Meanwhile, the potential therapeutic value of HTB50-2 was evaluated in BALB/c mice by orthotopic transplantation. Transcriptome sequencing was conducted to explore the FOS-like antigen 2 (FOSL2) gene, and its role in ferroptosis was verified by Western blot and immunohistochemistry. The association of FOSL2 and ferroptosis-related genes was analyzed using NetworkAnalyst databases, and a TF-Gene interaction network was constructed.

resultsFerroptosis was found to be induced in TNBC cells by HTB50-2. Furthermore, HTB50-2 inhibited tumor development by inducing ferroptosis in TNBC in vivo. Mechanistically, we demonstrated that a transcription factor FOSL2 mediated ferroptosis by HTB50-2. Additionally, it was found that Forkhead box C1 (FOXC1) was regulated by FOSL2 and correlated with ferroptosis.

conclusionOur data suggest that HTB50-2 exerts its anti-cancer properties by ferroptosis via FOSL2/FOXC1 signaling pathway. Hence, HTB50-2 has an important application potential in the treatment of TNBC.

Indexed as

Antineoplastic AgentsFerroptosisFos-Related Antigen-2Triple Negative Breast NeoplasmsAnimalsCell Line, TumorCell MovementCell ProliferationDrug Screening Assays, AntitumorFemaleHumansMiceMice, Inbred BALB CMice, NudeSignal TransductionAntineoplastic AgentsFOSL2 protein, humanFos-Related Antigen-2CGsferroptosisFOSL2FOXC1.migrationTNBC

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.