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2000
Volume 32, Issue 32
  • ISSN: 0929-8673
  • E-ISSN: 1875-533X

Abstract

Background

The 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 , in Triple-Negative Breast Cancer (TNBC). Moreover, we also studied its potential mechanisms.

Methods

The 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.

Results

Ferroptosis was found to be induced in TNBC cells by HTB50-2. Furthermore, HTB50-2 inhibited tumor development by inducing ferroptosis in TNBC . 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.

Conclusion

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

© 2025 Bentham Science Publishers
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2024-08-09
2025-10-26

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HTB50-2 Inhibits Growth and Migration of Triple-negative Breast Cancer via FOSL2/FOXC1 Signaling Axis and Subsequent Ferroptosis
Curr. Med. Chem. 32, 7082 (2025); https://doi.org/10.2174/0109298673306760240802062909
/content/journals/cmc/10.2174/0109298673306760240802062909
/content/journals/cmc/10.2174/0109298673306760240802062909
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  • Article Type:     Research Article
Keyword(s): CGs; ferroptosis; FOSL2; FOXC1; migration; TNBC

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