BIRO1, a cell-permeable BH3 peptide, promotes mitochondrial fragmentation and death of retinoblastoma cells.

Abstract

UNLABELLED:

Retinoblastoma is the most common pediatric intraocular neoplasm. While retinoblastoma development requires the inactivation of both alleles of the retinoblastoma tumor suppressor gene (RB1) in the developing retina, additional genomic changes are involved in tumor progression, which progressively lead to resistance of tumor cells to death. Therapeutics acting at very downstream levels of death signaling pathways should therefore be interesting in killing retinoblastoma cells. The BH3-only proteins promote apoptosis by modulating the interaction between the pro- and antiapoptotic members of the BCL2 protein family, and this effect can be recapitulated by the BH3 domains. This report analyzes the effect of various BH3 peptides, corresponding to different BH3-only proteins, on two retinoblastoma cell lines, Y79 and WERI-Rb, as well as on the photoreceptor cell line 661W. The BH3 peptide BIRO1, derived from the BCL2L11 death domain, was very effective in promoting Y79 and WERI-Rb cell death without affecting the 661W photoreceptor cells. This cell death was efficient even in absence of BAX and was shown to be caspase independent. While ROS production or AIF release was not detected from mitochondria of treated cells, BIRO1 initiated mitochondria fragmentation in a short period of time following treatment.

IMPLICATIONS:

The BIRO1 peptide is highly effective at killing retinoblastoma cells and has potential as a peptidomimetic.

• Authors: Nathalie Allaman-Pillet, Anne Oberson, Daniel F Schorderet
• Journal: Molecular cancer research : MCR (Mol Cancer Res) Vol. 13 Issue 1 Pg. 86-97 (Jan 2015) ISSN: 1557-3125 [Electronic] United States
• PMID: 25143432 (Publication Type: Journal Article)
• Copyright: ©2014 American Association for Cancer Research.

Chemical References

• Apoptosis Regulatory Proteins
• BCL2L11 protein, human
• Bax protein (53-86)
• Bcl-2-Like Protein 11
• Bcl2l11 protein, mouse
• Membrane Proteins
• Peptide Fragments
• Proto-Oncogene Proteins
• Proto-Oncogene Proteins c-bcl-2
• Retinoblastoma Protein
• Caspases

Topics

• Animals
• Apoptosis (drug effects, genetics)
• Apoptosis Regulatory Proteins (administration & dosage, genetics)
• Bcl-2-Like Protein 11
• Caspases (genetics)
• Cell Line, Tumor
• Cell Survival (drug effects)
• Humans
• Membrane Proteins (administration & dosage, genetics)
• Mice
• Mice, Transgenic
• Mitochondria (drug effects, genetics, pathology)
• Peptide Fragments (administration & dosage, genetics)
• Proto-Oncogene Proteins (administration & dosage, genetics)
• Proto-Oncogene Proteins c-bcl-2 (biosynthesis, genetics)
• Retinoblastoma (genetics, pathology)
• Retinoblastoma Protein (genetics)
• Signal Transduction (drug effects)