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Natural scaffolds in anticancer therapy and precision medicine

Authors:	Aloran Mazumder Claudia Cerella Marc Diederich

Institution:	1. Department of Pharmacy, College of Pharmacy, Seoul National University, Seoul 151-742, South Korea;2. Laboratoire de Biologie Moléculaire et Cellulaire du Cancer, Hôpital Kirchberg, 9, rue Edward Steichen, L-2540 Luxembourg, Luxembourg

Abstract:	The diversity of natural compounds is essential for their mechanism of action. The source, structures and structure activity relationship of natural compounds contributed to the development of new classes of chemotherapy agents for over 40?years. The availability of combinatorial chemistry and high-throughput screening has fueled the challenge to identify novel compounds that mimic nature's chemistry and to predict their macromolecular targets. Combining conventional and targeted therapies helped to successfully overcome drug resistance and prolong disease-free survival. Here, we aim to provide an overview of preclinical investigated natural compounds alone and in combination to further improve personalization of cancer treatment.

Keywords:	Natural compounds Chemotherapy Targeted therapy Precision medicine AM allyl mercaptan AML acute myeloid leukemia AP-1 activator protein-1 Bcl-2 B-cell lymphoma-2 Bcl-xL B cell lymphoma-extra large BA boswellic acid CDC cell division cycle CGs cardiac glycosides CML chronic myeloid leukemia COX-2 cyclooxygenase-2 CRPC castration-resistant prostate cancer CSC cancer stem cells DNMT DNA methyltransferase DADS diallyl disulfides DATS diallyl trisulfide DATTS diallyl tetrasulfide DBTTS di-benzyl tetrasulfide DIM 3 3′–diindolylmethane E2F elongation factor 2 EGCG epigallocatechin gallate EGF epithelial growth factor eIF4E eukaryotic translation initiation factor 4E EMT epithelial-mesenchymal transition ER estrogen receptor ErbB2 EGFR-related protein B2 ERK extracellular signal-regulated kinase FAK focal adhesion kinase HDAC histone deacetylases HER human estrogen receptor HIF hypoxic inducible factor HSP-90 heat shock protein-90 HUVECs human umbilical vein endothelial cells I3C indole-3-carbinol IkBα inhibitor of kappa B IRES internal ribosome entry sites Keap1 Kelch-like ECH-associated protein 1 MMP Matrix metallopeptidase Mcl-1 myeloid cell leukemia-1 MD2 myeloid differentiation 2 MGMT 6 MMP mitochondrial membrane potential NAC NKA sodium-potassium ATPase NF-κB nuclear factor-κB NRF2 nuclear factor (erythroid-derived 2)-like-2 factor NPC nasopharyngeal carcinoma cells NSCLC non-small cell lung cancer OA oleanolic acid OSC Organosulfur compounds PARP-1 poly-(ADP-ribosyl)polymerase-1 PKC protein kinase C ROS reactive oxygen species SAMC S-allylmercaptocysteine TKI tyrosine kinase inhibitor TLR4 toll-like receptor 4 12-TPA TSA trichostatin A UPR unfolded protein response UA ursolic acid VPA valproic acid XIAP X-linked inhibitor of apoptosis
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