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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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