ZFIN ID: ZDB-PUB-170214-64
A Small Molecule that Induces Intrinsic Pathway Apoptosis with Unparalleled Speed
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.
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.
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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.
ADDITIONAL INFORMATION