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Volume 30
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10.3390/molecules30173634
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This is an early access version, the complete PDF, HTML, and XML versions will be available soon.
Article

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

by
Wenwen Pang
1,2,†,
Xiang Li
3,†,
Suying Yan
4,†,
Junshi Zhang
5,
Ping Wu
1,
Haiyang Yu
6,
Bowei Zhang
3,* and
Chunze Zhang
7,8,9,*
1
Department of Clinical Laboratory, Tianjin Union Medical Center, Nankai University, Tianjin 300071, China
2
Tianjin Integrative Traditional Chinese and Western Medicine Oncology Institute, Tianjin 300121, China
3
School of Medicine, Nankai University, Tianjin 300071, China
4
School of Integrative Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China
5
Department of Hematology, Oncology Center, Tianjin Union Medical Center, Nankai University, Tianjin 300071, China
6
State Key Laboratory of Component-based Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China
7
Department of Colorectal Surgery, Tianjin Union Medical Center, Nankai University, Tianjin 300071, China
8
The Institute of Translational Medicine, Tianjin Union Medical Center, Nankai University, Tianjin 300071, China
9
Tianjin Institute of Coloproctology, Tianjin 300121, China
*
Authors to whom correspondence should be addressed.
†
These authors contributed equally to this work.
Molecules 2025, 30(17), 3634; https://doi.org/10.3390/molecules30173634
Submission received: 19 July 2025 / Revised: 2 September 2025 / Accepted: 3 September 2025 / Published: 5 September 2025
(This article belongs to the Special Issue Pharmacological Effects of Natural Products: Antioxidant, Anti-Inflammatory and Anticancer Activities)
Versions Notes

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.
Keywords: bufalin; colorectal cancer; liver metastasis; de novo fatty acid synthesis; PI3K/AKT-mediated SREBP1/FASN pathway bufalin; colorectal cancer; liver metastasis; de novo fatty acid synthesis; PI3K/AKT-mediated SREBP1/FASN pathway

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MDPI and ACS Style

Pang, W.; Li, X.; Yan, S.; Zhang, J.; Wu, P.; Yu, H.; Zhang, B.; Zhang, C. Bufalin Suppresses Colorectal Cancer Liver Metastasis by Inhibiting De Novo Fatty Acid Synthesis via the PI3K/AKT-Mediated SREBP1/FASN Pathway. Molecules 2025, 30, 3634. https://doi.org/10.3390/molecules30173634

AMA Style

Pang W, Li X, Yan S, Zhang J, Wu P, Yu H, Zhang B, Zhang C. Bufalin Suppresses Colorectal Cancer Liver Metastasis by Inhibiting De Novo Fatty Acid Synthesis via the PI3K/AKT-Mediated SREBP1/FASN Pathway. Molecules. 2025; 30(17):3634. https://doi.org/10.3390/molecules30173634

Chicago/Turabian Style

Pang, Wenwen, Xiang Li, Suying Yan, Junshi Zhang, Ping Wu, Haiyang Yu, Bowei Zhang, and Chunze Zhang. 2025. "Bufalin Suppresses Colorectal Cancer Liver Metastasis by Inhibiting De Novo Fatty Acid Synthesis via the PI3K/AKT-Mediated SREBP1/FASN Pathway" Molecules 30, no. 17: 3634. https://doi.org/10.3390/molecules30173634

APA Style

Pang, W., Li, X., Yan, S., Zhang, J., Wu, P., Yu, H., Zhang, B., & Zhang, C. (2025). Bufalin Suppresses Colorectal Cancer Liver Metastasis by Inhibiting De Novo Fatty Acid Synthesis via the PI3K/AKT-Mediated SREBP1/FASN Pathway. Molecules, 30(17), 3634. https://doi.org/10.3390/molecules30173634

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