title: Multi-Leu PACE4 Inhibitor Retention within Cells Is PACE4 Dependent and a Prerequisite for Antiproliferative Activity.
abstract: The overexpression as well as the critical implication of the proprotein convertase PACE4 in prostate cancer progression has been previously reported and supported the development of peptide inhibitors. The multi-Leu peptide, a PACE4-specific inhibitor, was further generated and its capability to be uptaken by tumor xenograft was demonstrated with regard to its PACE4 expression status. To investigate whether the uptake of this inhibitor was directly dependent of PACE4 levels, uptake and efflux from cancer cells were evaluated and correlations were established with PACE4 contents on both wild type and PACE4-knockdown cell lines. PACE4-knockdown associated growth deficiencies were established on the knockdown HepG2, Huh7, and HT1080 cells as well as the antiproliferative effects of the multi-Leu peptide supporting the growth capabilities of PACE4 in cancer cells.
authors.affiliation: Institut de Pharmacologie de Sherbrooke, Université de Sherbrooke, Sherbrooke, QC, Canada J1H 5N4 ; Department of Surgery/Urology Division, Université de Sherbrooke, Sherbrooke, QC, Canada J1H 5N4.
authors.forename: Frédéric
authors.identifier: 0000-0001-7785-5881
authors.initials: F
authors.lastname: Couture
authors.affiliation: Institut de Pharmacologie de Sherbrooke, Université de Sherbrooke, Sherbrooke, QC, Canada J1H 5N4 ; Department of Surgery/Urology Division, Université de Sherbrooke, Sherbrooke, QC, Canada J1H 5N4.
authors.forename: Kévin
authors.initials: K
authors.lastname: Ly
authors.affiliation: Institut de Pharmacologie de Sherbrooke, Université de Sherbrooke, Sherbrooke, QC, Canada J1H 5N4 ; Department of Surgery/Urology Division, Université de Sherbrooke, Sherbrooke, QC, Canada J1H 5N4.
authors.forename: Christine
authors.initials: C
authors.lastname: Levesque
authors.affiliation: Institut de Pharmacologie de Sherbrooke, Université de Sherbrooke, Sherbrooke, QC, Canada J1H 5N4 ; Department of Surgery/Urology Division, Université de Sherbrooke, Sherbrooke, QC, Canada J1H 5N4.
authors.forename: Anna
authors.initials: A
authors.lastname: Kwiatkowska
authors.affiliation: Department of Surgery/Urology Division, Université de Sherbrooke, Sherbrooke, QC, Canada J1H 5N4 ; Department of Nuclear Medicine and Radiobiology, Centre d'Imagerie Moléculaire de Sherbrooke, Centre de Recherche du Centre Hospitalier Universitaire de l'Université de Sherbrooke, Sherbrooke, QC, Canada J1H 5N4.
authors.forename: Samia
authors.initials: S
authors.lastname: Ait-Mohand
authors.affiliation: Institut de Pharmacologie de Sherbrooke, Université de Sherbrooke, Sherbrooke, QC, Canada J1H 5N4 ; Department of Surgery/Urology Division, Université de Sherbrooke, Sherbrooke, QC, Canada J1H 5N4.
authors.forename: Roxane
authors.initials: R
authors.lastname: Desjardins
authors.affiliation: Institut de Pharmacologie de Sherbrooke, Université de Sherbrooke, Sherbrooke, QC, Canada J1H 5N4 ; Department of Nuclear Medicine and Radiobiology, Centre d'Imagerie Moléculaire de Sherbrooke, Centre de Recherche du Centre Hospitalier Universitaire de l'Université de Sherbrooke, Sherbrooke, QC, Canada J1H 5N4.
authors.forename: Brigitte
authors.initials: B
authors.lastname: Guérin
authors.affiliation: Institut de Pharmacologie de Sherbrooke, Université de Sherbrooke, Sherbrooke, QC, Canada J1H 5N4 ; Department of Surgery/Urology Division, Université de Sherbrooke, Sherbrooke, QC, Canada J1H 5N4.
authors.forename: Robert
authors.initials: R
authors.lastname: Day
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D004791:Enzyme Inhibitors / Q000008:administration & dosage*; D006801:Humans; D051379:Mice; D009369:Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D043484:Proprotein Convertases / Q000037:antagonists & inhibitors / Q000096:biosynthesis* / Q000235:genetics; D012697:Serine Endopeptidases / Q000096:biosynthesis* / Q000235:genetics; D023041:Xenograft Model Antitumor Assays
chemical_list: D004791:Enzyme Inhibitors; C080654:PCSK6 protein, human; D043484:Proprotein Convertases; D012697:Serine Endopeptidases