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 parasite 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 1(mTORC1)/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.

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

Central European Institute of Technology Brno University of Technology Brno 60200 Czech Republic

Department of Chemistry and Biochemistry Mendel University in Brno Brno 61300 Czech Republic

Department of Chemistry Faculty of Science University of Hradec Kralove Hradec Kralove 50003 Czech Republic

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

Malaysia Japan International Institute of Technology University Teknologi Malaysia Kuala Lumpur 50200 Malaysia

School of Food and Biological Engineering Hefei University of Technology Hefei 230009 China

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