a Engineering Center of Innovative Veterinary Drugs, Center for Veterinary Drug Research and Evaluation, Ministry of Education Joint International Research Laboratory of Animal Health and Food Safety, College of Veterinary Medicine, Nanjing Agricultural University, Nanjing, 210095, China;
b Animal-Derived Food Safety Innovation Team, Anhui Province Key Lab of Veterinary Pathobiology and Disease Control, College of Animal Science and Technology, Anhui Agricultural University, Hefei, 230036, China;
c School of Food and Biological Engineering, Hefei University of Technology, Hefei, 230009, China d Department of Chemistry and Biochemistry, Mendel University in Brno, Brno, 613 00, Czech Republic e Central European Institute of Technology, Brno University of Technology, Brno, 602 00, Czech Republic f Department of Chemistry, Faculty of Science, University of Hradec Kralove, Hradec Kralove, 50003, Czech Republic g Malaysia-Japan International Institute of Technology (MJIIT), University Teknologi Malaysia, Kuala Lumpur, 50200, Malaysia
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This work was supported by the National Natural Science Foundation of China (Grant No.: 32172918), the project funded by the Priority Academic Program Development (PAPD) of Jiangsu Higher Education Institutions, China, and the Key Projects of Natural Science Foundation of Anhui Provincial Department of Education, China (Grant No.: 2023AH051017) and the Anhui Agricultural University Talent Research Grant Project (Project No.: RC393302).
The small-molecule alkaloid halofuginone (HF) is obtained from febrifugine. Recent studies on HF have aroused widespread attention owing to its universal range of noteworthy biological activities and therapeutic functions, which range from protozoan infections and fibrosis to autoimmune diseases. In particular, HF is believed to play an excellent anticancer role by suppressing the proliferation, adhesion, metastasis, and invasion of cancers. This review supports the goal of demonstrating various anticancer effects and molecular mechanisms of HF. In the studies covered in this review, the anticancer molecular mechanisms of HF mainly included Transforming growth factor-β (TGF-β)/Smad-3/ Nuclear factor erythroid 2-related factor 2 (Nrf2), Serine/Threonine Kinase Proteins (Akt)/mechanistic target of rapamycin complex A1(mTORCA1)/ Wingless/Integrated (Wnt)/β-catenin, the exosomal MicroRNA-31 (miR-31)/ Histone Deacetylase 2 (HDAC2) signaling pathway, and the interaction of the extracellular matrix (ECM) and immune cells. Notably, HF, as a novel type of adenosine triphosphate (ATP)-dependent inhibitor that is often combined with Prolyl transfer RNA synthetase (ProRS) and amino acid starvation therapy (AAS) to suppress the formation of ribosome, further exerts a significant effect on the tumor microenvironment (TME). Additionally, the combination of HF with other drugs or therapies obtained universal attention. Our results showed that HF has significant potential for clinical cancer treatment.
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