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

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State: Public
Version: author
Serval ID
serval:BIB_8C6A4FC7395F
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
BIRO1, a cell-permeable BH3 peptide, promotes mitochondrial fragmentation and death of retinoblastoma cells.
Journal
Molecular Cancer Research
Author(s)
Allaman-Pillet N., Oberson A., Schorderet D.F.
ISSN
1557-3125 (Electronic)
ISSN-L
1541-7786
Publication state
Published
Issued date
2015
Peer-reviewed
Oui
Volume
13
Number
1
Pages
86-97
Language
english
Notes
Publication types: Journal Article
Abstract
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.
Pubmed
Web of science
Open Access
Yes
Create date
14/10/2014 16:58
Last modification date
20/08/2019 15:50
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