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Bufalin Suppresses Colorectal Cancer Liver Metastasis by Inhibiting De Novo Fatty Acid Synthesis via the PI3K/AKT-Mediated SREBP1/FASN Pathway

Published:5 September 2025 DOI: 10.3390/molecules30173634 PMID: 40942159
Wenwen Pang,?Xiang Li,?Suying Yan,?Junshi Zhang,?Ping Wu,?Haiyang Yu,?Bowei Zhang,?Chunze Zhang

Abstract

Background: Colorectal cancer (CRC) is the third most common cancer worldwide, with liver metastasis being the leading cause of mortality. De novo fatty acid synthesis plays a critical role in CRC progression and metastasis. Bufalin, a cardiotonic steroid isolated from toad skin, has demonstrated anticancer activity in multiple preclinical models. However, the mechanisms underlying its suppression of CRC metastasis and modulation of fatty acid synthesis remain to be elucidated.

Methods: The effects of bufalin on CRC cell proliferation, migration, and apoptosis were assessed via colony formation, wound healing, and flow cytometry assays. Transcriptome analysis identified bufalin-affected pathways, with changes in gene and protein expression. FASN protein levels were quantified using ELISA.

Results: Bufalin inhibited proliferation and migration of CRC cells and induced the apoptosis of LoVo and HCT8 cells. Transcriptome analysis highlighted lipid metabolism pathways as potential mediators of bufalin's anti-metastatic activity. Notably, bufalin reduced the expression of fatty acid synthase (FASN) and suppressed CRC metastasis. In vivo experiments demonstrated that bufalin attenuated CRC progression and liver metastasis by inhibiting de novo fatty acid synthesis through the PI3K/AKT-mediated SREBP1/FASN pathway.

Conclusions: Bufalin inhibits de novo fatty acid synthesis via the PI3K/AKT-mediated SREBP1/FASN pathway, suppressing CRC progression and liver metastasis.

Substances (4)

Materials
Procduct Name CAS Molecular Formula Supplier Price
Bufalin 465-21-4 C24H34O4 284 suppliers $31.00-$2900.00
Bufalin 465-21-4 C24H34O4 284 suppliers $31.00-$2900.00
Bufalin 465-21-4 C24H34O4 284 suppliers $31.00-$2900.00
Bufalin 465-21-4 C24H34O4 284 suppliers $31.00-$2900.00

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