Growth inhibition and induction of apoptosis in NB4 promyelocytic leukemia cells by trypsin inhibitor from sweet potato storage roots

J Agric Food Chem. 2007 Apr 4;55(7):2548-53. doi: 10.1021/jf063008m. Epub 2007 Mar 1.

Abstract

The objective of this study was to investigate the antiproliferative effect and the mechanism of trypsin inhibitor (TI) from sweet potato [Ipomoea batatas (L.) Lam. 'Tainong 57'] storage roots on NB4 promyelocytic leukemia cells. The results showed that TI inhibited cellular growth of NB4 promyelocytic leukemia cells in a time-dependent and dose-dependent manner, and treatment for 72 h induced a marked inhibition of cellular growth, showing an IC50 of 57.1 +/- 8.26 microg/mL. TI caused cell cycle arrest at the G1 phase as determined by flow cytometric analysis and apoptosis as shown by DNA laddering. TI-induced cell apoptosis involved p53, Bcl-2, Bax, and cytochrome c protein in NB4 cells. P53 and Bax proteins were accumulated, and antiapoptotic molecule Bcl-2 was decreased in the tested cells in a time-dependent manner during TI treatment. TI also induced a substantial release of cytochrome c from the mitochondria into the cytosol. Hence, TI induced apoptosis in NB4 cells through a mitochondria-dependent pathway, which was associated with the activation of caspase-3 and -8. These results demonstrated that TI induces NB4 cell apoptosis through the inhibition of cell growth and the activation of the pathway of caspase-3 and -8 cascades.

MeSH terms

  • Apoptosis / drug effects*
  • Caspases / metabolism
  • Cell Cycle Proteins / analysis
  • Cell Division / drug effects*
  • Cell Line, Tumor
  • DNA Fragmentation / drug effects
  • Flow Cytometry
  • Humans
  • Ipomoea batatas / chemistry*
  • Leukemia, Promyelocytic, Acute
  • Plant Tubers / chemistry*
  • Trypsin Inhibitors / isolation & purification
  • Trypsin Inhibitors / pharmacology*

Substances

  • Cell Cycle Proteins
  • Trypsin Inhibitors
  • Caspases