Halofuginone for cancer treatment: A systematic review of efficacy and molecular mechanisms. (November 2022)

• Record Type: Journal Article
• Authors: Mi, Li; Zhang, Yujie; Su, Anping; Tang, Minghai; Xing, Zhichao; He, Ting; Wu, Wenshuang; Li, Zhihui
• Is Part Of: Journal of functional foods. Volume 98(2022)
• Publication Date: 2022-11
• Subjects: Natural product -- Halofuginone -- Anticancer activity -- Molecular mechanism -- EPRS -- AAR; AAR amino acid starvation response -- AIDS acquired immunodeficiency syndrome -- AMPK AMP-activated protein kinase -- AP-1 activator protein-1 -- ATG autophagy -- ATS artemisinin -- Bcl-2 B-cell lymphoma 2 -- BMPs bone morphogenetic proteins -- CDK2 cyclin-dependent kinases 2 -- cSCC cutaneous squamous cell carcinoma -- DLTs dose-limiting toxicities -- ECM extracellular matrix -- Egr-1 early growth response protein-1 -- EMT epithelial-mesenchymal transition -- EPRS glutamyl-prolyl-tRNA synthetase -- ERK1/2 extracellular signal-regulated kinase 1/2 -- GLUT1 the glucose transporter type 1 -- HCC hepatocellular carcinoma -- HDAC2 histone deacetylase 2 -- HF halofuginone -- IAPs inhibitors of apoptosis -- IC50 half-maximal inhibitory -- JNKs c-Jun N-terminal kinases -- KSHV-LANA Kaposi sarcoma herpesvirus-latency associated nuclear antigen-1 -- LKB1 liver kinase B1 -- MAPK mitogen-activated protein kinases -- Mcl-1 myeloid cell leukemia-1 -- MDSCs myeloid-derived suppressor cells -- MMP-2 matrix metalloproteinase-2 -- MMP-9 matrix metalloproteinase-9 -- MTD maximum tolerated dose -- mTOR mammalian target of rapamycin -- mTORC1 mammalian target of rapamycin complex 1 -- MYC myelocytomatosis oncogene -- NF-κB nuclear transcription factor-kappa B -- Nrf2 nuclear factor E2-related factor 2 -- PARP poly-ADP-ribose polymerases -- PI3K The phosphatidylinositol 3-kinase -- ROS reactive oxygen species -- SARS-CoV-2 severe acute respiratory syndrome coronavirus 2 -- Smad small mother against decapentaplegic -- STAT3 signal transducer and activator of transcription 3 -- STMN1 stathmin 1 -- TAMs tumor-associated macrophages -- TFEB transcription factor EB -- TGF-β transforming growth factor beta -- TME tumor microenvironment -- TMPRSS2 transmembrane serine protease 2 -- TSP-1 thrombospondin-1 -- ULK1 Unc-51 like autophagy activating kinase 1 -- VEGF vascular endothelial growth factor -- VHL von-Hippel-Lindau -- VSV vesicular stomatitis virus; Functional foods -- Analysis -- Periodicals; Food -- Biotechnology -- Periodicals; Nutrition -- Periodicals; 613.2
• DOI: 10.1016/j.jff.2022.105237
• Languages: English
• ISSNs: 1756-4646

Abstract

Graphical abstract: Highlights: We provide a comprehensive review of the most recent anticancer studies reported for Halofuginone (HF). HF exhibits significant anticancer activity and synergistic effects in chemotherapy/radiotherapy/virus for the treatment of various cancers in vitro and in vivo. HF could induce cell cycle arrest, apoptosis and autophagy, inhibit cell proliferation, invasion, migration and angiogenesis, and disturb the tumor microenvironment in tumor cells. The anticancer effect of HF might be associated with the induction of the amino acid starvation response by HF in response to the inhibition of glutamyl-prolyl-tRNA synthetase. Abstract: Cancer is still considered a "hopeless case", which seriously endangers human health. Therefore, it is of great significance to research and develop novel anticancer drugs. Active natural products play an important role in anticancer drug discovery by providing lead compounds. Halofuginone (HF), as a derivative of febrifugine, an alkaloid originally isolated from the plant Dichroa febrifuga, is used for the prevention and treatment of coccidiosis and malaria in poultry. In recent years, HF has shown excellent anticancer activity and great clinical potential for treating various cancers. Despite enormous progress, a thorough elaboration of the proposed mechanism and mode of action is absent. Herein, we provide a comprehensive review of the most recent anticancer studies reported for HF and a rationale for further exploring the potential application of HF in overcoming cancer in the future.