PUBLICATION
A Small Molecule that Induces Intrinsic Pathway Apoptosis with Unparalleled Speed
- Authors
- Palchaudhuri, R., Lambrecht, M.J., Botham, R.C., Partlow, K.C., van Ham, T.J., Putt, K.S., Nguyen, L.T., Kim, S.H., Peterson, R.T., Fan, T.M., Hergenrother, P.J.
- ID
- ZDB-PUB-170214-64
- Date
- 2015
- Source
- Cell Reports 13: 2027-36 (Journal)
- Registered Authors
- Peterson, Randall
- Keywords
- none
- MeSH Terms
-
- Animals
- Apoptosis*/drug effects
- Caspase 3/chemistry
- Caspase 3/genetics
- Caspase 3/metabolism
- Cell Line, Tumor
- Complement C8/deficiency
- Complement C8/genetics
- Cyclopentanes/chemistry*
- Cyclopentanes/pharmacokinetics
- Cyclopentanes/toxicity
- Embryo, Nonmammalian/metabolism
- Fas-Associated Death Domain Protein/deficiency
- Fas-Associated Death Domain Protein/genetics
- Fluorenes/chemistry*
- Fluorenes/pharmacokinetics
- Fluorenes/toxicity
- Half-Life
- Humans
- Jurkat Cells
- Membrane Potential, Mitochondrial/drug effects
- Mice
- Mice, Inbred C57BL
- Mitochondria/metabolism
- RNA Interference
- RNA, Small Interfering/metabolism
- Zebrafish
- PubMed
- 26655912 Full text @ Cell Rep.
Citation
Palchaudhuri, R., Lambrecht, M.J., Botham, R.C., Partlow, K.C., van Ham, T.J., Putt, K.S., Nguyen, L.T., Kim, S.H., Peterson, R.T., Fan, T.M., Hergenrother, P.J. (2015) A Small Molecule that Induces Intrinsic Pathway Apoptosis with Unparalleled Speed. Cell Reports. 13:2027-36.
Abstract
Apoptosis is generally believed to be a process that requires several hours, in contrast to non-programmed forms of cell death that can occur in minutes. Our findings challenge the time-consuming nature of apoptosis as we describe the discovery and characterization of a small molecule, named Raptinal, which initiates intrinsic pathway caspase-dependent apoptosis within minutes in multiple cell lines. Comparison to a mechanistically diverse panel of apoptotic stimuli reveals that Raptinal-induced apoptosis proceeds with unparalleled speed. The rapid phenotype enabled identification of the critical roles of mitochondrial voltage-dependent anion channel function, mitochondrial membrane potential/coupled respiration, and mitochondrial complex I, III, and IV function for apoptosis induction. Use of Raptinal in whole organisms demonstrates its utility for studying apoptosis in vivo for a variety of applications. Overall, rapid inducers of apoptosis are powerful tools that will be used in a variety of settings to generate further insight into the apoptotic machinery.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping