Conjugates of cytochrome c and antennapedia peptide activate apoptosis and inhibit proliferation of HeLa cancer cells

Imesch,Patrick; Scheiner,David; Szabo,Emese; Fink,Daniel; Fedier,André

doi:10.3892/etm.2013.1205

Conjugates of cytochrome c and antennapedia peptide activate apoptosis and inhibit proliferation of HeLa cancer cells

Authors:
- Patrick Imesch
- David Scheiner
- Emese Szabo
- Daniel Fink
- André Fedier
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Affiliations: Department of Gynecology, University Hospital Zurich, Zurich CH-8091, Switzerland
Published online on: July 4, 2013 https://doi.org/10.3892/etm.2013.1205
Pages: 786-790

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Abstract

Polycationic cell-penetrating peptides (CPPs) deliver macromolecules into cells without losing the functional properties of the cargoed macromolecule. The aim of this study was to determine whether exogenous cytochrome c is delivered to HeLa cervical carcinoma cells by the CPP antennapedia (Antp) and activates apoptosis. HeLa cervical carcinoma cells were treated with conjugated Antp-SMCC‑cytochrome c (cytochrome c chemically conjugated to Antp) or with non-conjugated Antp and cytochrome c. Sensitivity to the treatments was determined by the clonogenic assay (proliferation) and by immunoblot analysis (apoptosis activation). We report that conjugated Antp-SMCC-cytochrome c activated apoptosis in HeLa cells as demonstrated by poly (ADP-ribose) polymerase 1 (PARP-1) cleavage and inhibited their proliferation. The Antp‑SMCC-cytochrome c-induced apoptosis was inhibited by z-VAD-fmk, a pan‑caspase inhibitor peptide. Unconjugated Antp or cytochrome c demonstrated no inhibitory effect on survival and proliferation. Our results suggest that chemical coupling of cytochrome c to CPPs may present a possible strategy for delivering cytochrome c into cells and for activating apoptosis.

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