title: Conjugates of cytochromecand antennapedia peptide activate apoptosis and inhibit proliferation of HeLa cancer cells.
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 cytochromecis delivered to HeLa cervical carcinoma cells by the CPP antennapedia (Antp) and activates apoptosis. HeLa cervical carcinoma cells were treated with conjugated Antp-SMCC-cytochromec(cytochromecchemically conjugated to Antp) or with non-conjugated Antp and cytochromec. Sensitivity to the treatments was determined by the clonogenic assay (proliferation) and by immunoblot analysis (apoptosis activation). We report that conjugated Antp-SMCC-cytochromecactivated apoptosis in HeLa cells as demonstrated by poly (ADP-ribose) polymerase 1 (PARP-1) cleavage and inhibited their proliferation. The Antp-SMCC-cytochromec-induced apoptosis was inhibited by z-VAD-fmk, a pan-caspase inhibitor peptide. Unconjugated Antp or cytochromecdemonstrated no inhibitory effect on survival and proliferation. Our results suggest that chemical coupling of cytochromecto CPPs may present a possible strategy for delivering cytochromecinto cells and for activating apoptosis.
authors.affiliation: Department of Gynecology, University Hospital Zurich, Zurich CH-8091, Switzerland.
authors.forename: Patrick
authors.initials: P
authors.lastname: Imesch
authors.forename: David
authors.initials: D
authors.lastname: Scheiner
authors.forename: Emese
authors.initials: E
authors.lastname: Szabo
authors.forename: Daniel
authors.initials: D
authors.lastname: Fink
authors.forename: André
authors.initials: A
authors.lastname: Fedier
keywords: apoptosis; cell-penetrating peptides; cytochrome c; proliferation