Apoptosis and lysosome membrane permeabilization induction on breast cancer cells by an anticarcinogenic Bowman-Birk protease inhibitor from Vigna unguiculata seeds

Cancer Lett. 2010 Jul 1;293(1):73-81. doi: 10.1016/j.canlet.2009.12.017. Epub 2010 Feb 4.

Abstract

In this work, we report the effects of a Bowman-Birk protease inhibitor, the Black-Eyed Pea Trypsin/Chymotrypsin Inhibitor - BTCI, purified from Vigna unguiculata seeds, on the MCF-7 breast cancer cells. The treatment of MCF-7 with 200microM BTCI for 72h induced significant reduction of the cell viability and proliferation (arrest in S and G2/M phase). These cytostatic effects were accompanied by acute morphological modifications including the alteration of the nuclear morphology, plasma membrane fragmentation, cytoplasm disorganization, presence of double-membrane vesicles, mitochondrial swelling, and an increase in the size of lysosomes. Significative DNA fragmentation, annexin-V(+) cell number increase, mitochondrial membrane potential reduction, and cytoplasm acidification were also detected. All together, these cytostatic and cytotoxic results point out to BTCI-induced apoptosis cell death associated with severe cell morphological alterations and lysosome membrane permeabilization. Our study confirms the anticarcinogenic potential of Bowman-Birk protease inhibitors and identifies BTCI as a promising tool for drug developments aimed at the treatment of breast cancer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis / drug effects*
  • Breast Neoplasms / drug therapy*
  • Breast Neoplasms / metabolism
  • Breast Neoplasms / pathology
  • Cell Cycle / drug effects
  • Cell Growth Processes / drug effects
  • Cell Line, Tumor
  • Cell Membrane Permeability / drug effects
  • Cell Survival / drug effects
  • Fabaceae / chemistry*
  • Female
  • Humans
  • Lysosomes / drug effects*
  • Lysosomes / metabolism
  • Membrane Potential, Mitochondrial / drug effects
  • Microscopy, Fluorescence
  • Plant Proteins / isolation & purification
  • Plant Proteins / pharmacology
  • Seeds / chemistry
  • Trypsin Inhibitors / isolation & purification
  • Trypsin Inhibitors / pharmacology*

Substances

  • Plant Proteins
  • Trypsin Inhibitors
  • trypsin, chymotrypsin inhibitor, black-eyed pea