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Barnase as a new therapeutic agent triggering apoptosis in human cancer cells

Evelina Edelweiss1, Taras G Balandin, Julia L Ivanova

  • 1Shemyakin and Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Moscow, Russia. edelweiss.evelina@gmail.com

Plos One
|June 19, 2008
PubMed
Abstract

Insights

Barnase, a bacterial ribonuclease, shows potent anticancer activity against human cancer cells by inducing apoptosis. An immuno-RNase, scFv 4D5-dibarnase, targeting HER2-positive cells, demonstrated significantly enhanced cytotoxicity.

Area of Science:

  • Biochemistry
  • Molecular Biology
  • Oncology

Background:

  • Ribonucleases (RNases) are explored as non-mutagenic anticancer agents.
  • Mammalian RNases are often inhibited by cytoplasmic ribonuclease inhibitor (RI).

Purpose of the Study:

  • To investigate the anticancer potential of barnase, a bacterial RNase.
  • To evaluate the efficacy of a barnase-based immuno-RNase targeting HER2-positive cancer cells.

Main Methods:

  • Barnase cytotoxicity assessed via MTT assay on human carcinoma and leukemia cell lines.
  • Development and characterization of scFv 4D5-dibarnase, an immuno-RNase targeting HER2.
  • Analysis of apoptosis induction, including chromatin fragmentation and caspase-3 activation.

Main Results:

  • Barnase demonstrated RI resistance and potent cytotoxicity against various human cancer cell lines (IC(50) 0.2-82 microM).
  • scFv 4D5-dibarnase exhibited enhanced specificity and efficacy against HER2-positive cells (IC(50) = 1.8 nM).
  • Both agents induced apoptosis in SKOV-3 cells.

Conclusions:

  • Barnase is a potent cytotoxic agent for cancer cell targeting.
  • Immuno-RNase constructs like scFv 4D5-dibarnase offer significantly improved therapeutic potential.

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