Inhibition of leukemic U937 cell growth by induction of apoptosis, cell cycle arrest and suppression of VEGF, MMP-2 and MMP-9 activities by cytotoxin protein NN-32 purified from Indian spectacled cobra (Naja naja) venom

Toxicon. 2013 Apr:65:1-4. doi: 10.1016/j.toxicon.2013.01.004. Epub 2013 Jan 18.

Abstract

A cytotoxin NN-32 (6.7 kDa) from Indian cobra (Naja naja) venom inhibited human leukemic U937 cell growth as observed by Trypan blue dye exclusion method and cytotoxicity was confirmed by MTT assay. NN-32 induced apoptosis of U937 cell and cell cycle arrest of sub-G1 phase were revealed by FACS analysis. Increased Bax/Bcl-2 ratio, increased caspase 3 and 9 activities, cleaved PARP, decreased VEGF, MMP-2 and MMP-9 activities were observed after NN-32 treatment of U937 cell. Antileukemic activity of NN-32 on U937 cell may be due to activation of apoptosis, arresting cell cycle and antiangiogenesis activities.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antineoplastic Agents / isolation & purification
  • Antineoplastic Agents / pharmacology*
  • Apoptosis / drug effects
  • Cell Cycle Checkpoints / drug effects
  • Cell Proliferation / drug effects*
  • Cobra Cardiotoxin Proteins / isolation & purification
  • Cobra Cardiotoxin Proteins / pharmacology*
  • Cytostatic Agents / isolation & purification
  • Cytostatic Agents / pharmacology*
  • Elapid Venoms / chemistry*
  • Elapidae
  • Humans
  • Matrix Metalloproteinase 2 / metabolism
  • Matrix Metalloproteinase 9 / metabolism
  • U937 Cells
  • Vascular Endothelial Growth Factor A / metabolism

Substances

  • Antineoplastic Agents
  • Cobra Cardiotoxin Proteins
  • Cytostatic Agents
  • Elapid Venoms
  • Vascular Endothelial Growth Factor A
  • Matrix Metalloproteinase 2
  • Matrix Metalloproteinase 9