Procaspase-3 Overexpression in Cancer: A Paradoxical Observation with Therapeutic Potential

Matthew W. Boudreau, Jessie Peh, Paul J. Hergenrother

Research output: Contribution to journalReview articlepeer-review


Many anticancer strategies rely on the promotion of apoptosis in cancer cells as a means to shrink tumors. Crucial for apoptotic function are executioner caspases, most notably caspase-3, that proteolyze a variety of proteins, inducing cell death. Paradoxically, overexpression of procaspase-3 (PC-3), the low-activity zymogen precursor to caspase-3, has been reported in a variety of cancer types. Until recently, this counterintuitive overexpression of a pro-apoptotic protein in cancer has been puzzling. Recent studies suggest subapoptotic caspase-3 activity may promote oncogenic transformation, a possible explanation for the enigmatic overexpression of PC-3. Herein, the overexpression of PC-3 in cancer and its mechanistic basis is reviewed; collectively, the data suggest the potential for exploitation of PC-3 overexpression with PC-3 activators as a targeted anticancer strategy.

Original languageEnglish (US)
Pages (from-to)2335-2348
Number of pages14
JournalACS chemical biology
Issue number11
StatePublished - Nov 15 2019

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine


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