Antitumor activity of NPB001-05, an orally active inhibitor of Bcr-Abl tyrosine kinase

Front Biosci (Elite Ed). 2011 Jun 1;3:1349-64. doi: 10.2741/e338.


Scientists are constantly searching for phytochemical compounds with anti-cancer activity. In this study, activity of plant extract NPB001-05 from Piper betle was tested on human chronic myelogenous leukemia (CML) xenograft models. NPB001-05 was active when dosed orally (500 mg/kg) once or twice a day in xenograft tumor models. NPB001-05 showed activity to T315I tumor xenograft, where imatinib failed to show antitumor activity. NPB001-05 showed no relevant toxicity in animal models during 2 weeks exposure to drug. Responsive tumor showed inhibition of tyrosine kinase activity with lowered Bcr-Abl protein levels and increased apoptosis. Microarray based transcription profiling studies demonstrated that both imatinib and NPB001-05 dysregulated imatinib- responsive genes. NPB001-05 showed additional genes selectively dysregulated from ER stress, PI3K/AKT, MAPK pathways. Additionally, we tested gene expression of PI3K, AKT1, JUN, CASP3 and DDIT3 in K562, BaF3P210(BCR-ABL) and BaF3 P210(BCR-ABLT315I) cell line treated for 6- and 12- hours with NPB001-05 and imatinib. The data indicates that NPB001-05 mediated cell death in K562 affects the function of ER stress. NPB001-05 shows antitumor activity with favorable toxicity profile.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Oral
  • Animals
  • Antineoplastic Agents / administration & dosage
  • Antineoplastic Agents / pharmacology*
  • Base Sequence
  • DNA Primers
  • Enzyme Inhibitors / administration & dosage
  • Enzyme Inhibitors / pharmacology*
  • Fusion Proteins, bcr-abl / antagonists & inhibitors*
  • Humans
  • Male
  • Mice
  • Mice, SCID
  • Plant Extracts / administration & dosage
  • Plant Extracts / pharmacology*
  • Protein-Tyrosine Kinases / antagonists & inhibitors*
  • Reverse Transcriptase Polymerase Chain Reaction


  • Antineoplastic Agents
  • DNA Primers
  • Enzyme Inhibitors
  • NPB001-05
  • Plant Extracts
  • Protein-Tyrosine Kinases
  • Fusion Proteins, bcr-abl