Lunasin, with an arginine-glycine-aspartic acid motif, causes apoptosis to L1210 leukemia cells by activation of caspase-3

Mol Nutr Food Res. 2010 Mar;54(3):406-14. doi: 10.1002/mnfr.200900073.

Abstract

Lunasin is a novel chemopreventive peptide featuring a cell adhesion motif composed of arginine-glycine-aspartate (RGD) which has been associated to cytotoxicity to established cell lines. The objectives of this study were to determine the effect of lunasin on the viability of L1210 leukemia cells and to understand the underlying mechanisms involved. Pure lunasin and lunasin enriched soy flour (LES) caused cytotoxicity to L1210 leukemia cells with IC(50) of 14 and 16 microM (lunasin equivalent), respectively. Simulated gastrointestinal digestion showed that 25% of the original amount of lunasin survived 3 h of pepsin digestion and 3% of lunasin remained after sequential pepsin-pancreatin digestion for a total of 6 h. Cell cycle analysis showed that lunasin caused a dose-dependent G2 cell cycle arrest and apoptosis. Treatment of L1210 leukemia cells with 1 mg/mL of LES for 18 h led to an increase in the amount of apoptotic cells from 2 to 40%. Compared to untreated cells, treatment with 1 mg/mL LES showed a 6-fold increase on the expressions of caspases-8 and -9, and and a 12-fold increase on the expression of caspase-3. These results showed for the first time that lunasin, a naturally occurring peptide containing an RGD motif, caused apoptosis to L1210 leukemia cells through caspase-3 activation.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Amino Acid Motifs
  • Animals
  • Antineoplastic Agents, Phytogenic / chemistry
  • Antineoplastic Agents, Phytogenic / metabolism
  • Antineoplastic Agents, Phytogenic / pharmacology*
  • Apoptosis / drug effects*
  • Caspase 3 / metabolism*
  • Caspase 8 / metabolism
  • Caspase 9 / metabolism
  • Cell Line, Tumor
  • Cell Survival / drug effects
  • Dose-Response Relationship, Drug
  • Drug Stability
  • Enzyme Activation
  • G2 Phase / drug effects
  • Hydrolases / metabolism
  • Inhibitory Concentration 50
  • Leukemia L1210 / drug therapy*
  • Leukemia L1210 / metabolism
  • Leukemia L1210 / pathology
  • Mice
  • Oligopeptides*
  • Phytotherapy
  • Plant Extracts / chemistry
  • Plant Extracts / isolation & purification
  • Plant Extracts / pharmacology
  • Soybean Proteins / chemistry
  • Soybean Proteins / metabolism
  • Soybean Proteins / pharmacology*
  • Time Factors

Substances

  • Antineoplastic Agents, Phytogenic
  • GM2S-1 protein, Glycine max
  • Oligopeptides
  • Plant Extracts
  • Soybean Proteins
  • arginyl-glycyl-aspartic acid
  • Hydrolases
  • Caspase 3
  • Caspase 8
  • Caspase 9