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Multi-Leu PACE4 Inhibitor Retention within Cells Is PACE4 Dependent and a Prerequisite for Antiproliferative Activity.

Couture F, Ly K, Levesque C, Kwiatkowska A, Ait-Mohand S, Desjardins R, Guérin B, Day R - Biomed Res Int (2015)

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

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.

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.

No MeSH data available.


Related in: MedlinePlus

Knockdown cell proliferation rates. Percentage of initial (24 h postseeding) metabolic activity determined on mirror plates every 24 h using XTT reagent for HepG2 (a), Huh7 (b), and HT1080 (c). Control cells are shown as plain line and knockdown cells as dashed lines. Data are means ± SEM of at least 3 independent experiments.
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fig2: Knockdown cell proliferation rates. Percentage of initial (24 h postseeding) metabolic activity determined on mirror plates every 24 h using XTT reagent for HepG2 (a), Huh7 (b), and HT1080 (c). Control cells are shown as plain line and knockdown cells as dashed lines. Data are means ± SEM of at least 3 independent experiments.

Mentions: It was previously demonstrated that PACE4 knockdown in DU145 and LNCaP prostate cancer cells was associated with markedly reduced cell growth rate both in vitro and in vivo [9]. Since PACE4 knockdowns in HepG2, Huh7, and HT1080 were never reported before, we sought to evaluate whether this growth phenotype was also observable. XTT proliferation assays were carried out to measure the proliferation rates of these cells compared to their respective control. As shown in Figure 2, cell growth was monitored on 96 h and shPACE4 reduced cell proliferation by 30% for HepG2, 45% for Huh7, and 35% for HT1080 after 96 h relative to the control cells. These growth rate reductions were however lower than those observed in the prostate cancer cells (i.e., reduction of about 50% of growth after 96 h) [9], indicating a relevant but yet inferior PACE4 dependance on their growth capabilities.


Multi-Leu PACE4 Inhibitor Retention within Cells Is PACE4 Dependent and a Prerequisite for Antiproliferative Activity.

Couture F, Ly K, Levesque C, Kwiatkowska A, Ait-Mohand S, Desjardins R, Guérin B, Day R - Biomed Res Int (2015)

Knockdown cell proliferation rates. Percentage of initial (24 h postseeding) metabolic activity determined on mirror plates every 24 h using XTT reagent for HepG2 (a), Huh7 (b), and HT1080 (c). Control cells are shown as plain line and knockdown cells as dashed lines. Data are means ± SEM of at least 3 independent experiments.
© Copyright Policy - open-access
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4465654&req=5

fig2: Knockdown cell proliferation rates. Percentage of initial (24 h postseeding) metabolic activity determined on mirror plates every 24 h using XTT reagent for HepG2 (a), Huh7 (b), and HT1080 (c). Control cells are shown as plain line and knockdown cells as dashed lines. Data are means ± SEM of at least 3 independent experiments.
Mentions: It was previously demonstrated that PACE4 knockdown in DU145 and LNCaP prostate cancer cells was associated with markedly reduced cell growth rate both in vitro and in vivo [9]. Since PACE4 knockdowns in HepG2, Huh7, and HT1080 were never reported before, we sought to evaluate whether this growth phenotype was also observable. XTT proliferation assays were carried out to measure the proliferation rates of these cells compared to their respective control. As shown in Figure 2, cell growth was monitored on 96 h and shPACE4 reduced cell proliferation by 30% for HepG2, 45% for Huh7, and 35% for HT1080 after 96 h relative to the control cells. These growth rate reductions were however lower than those observed in the prostate cancer cells (i.e., reduction of about 50% of growth after 96 h) [9], indicating a relevant but yet inferior PACE4 dependance on their growth capabilities.

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

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.

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.

No MeSH data available.


Related in: MedlinePlus