Anti-tumorigenic and platinum-sensitizing effects of apolipoprotein A1 and apolipoprotein A1 mimetic peptides in ovarian cancer

Title: Anti-tumorigenic and platinum-sensitizing effects of apolipoprotein A1 and apolipoprotein A1 mimetic peptides in ovarian cancer
Authors: Marinho, AT
Lu, H
Pereira, SA
Monteiro, E
Gabra, H
Recchi, C
Item Type: Journal Article
Abstract: Objective: Apolipoprotein A1 (ApoA1) is remarkably decreased in serum and ovarian tissues of ovarian cancer patients. ApoA1 and ApoA1 mimetic peptides can sequestrate pro-inflammatory phospholipids, some of which are known to activate a variety of oncogenic pathways. Besides, more intrinsic anti-tumorigenic properties, independent from interaction with lipids, have also been described for ApoA1. We aimed to disclose the effects of ApoA1 and a mimetic peptide on the malignant phenotype of ovarian cancer cells, particularly regarding cell viability, invasiveness and platinum sensitization. Methods: Cells viability was assessed by MTS assay. Extracellular matrix invasion was assessed by transwell and spheroid invasion assays. Western blotting was performed to evaluate the effect of test compounds on intracellular pathways. Sensitization assays were performed in vitro and in the biologically relevant in ovo chorioallantoic membrane model. Results: Both ApoA1 and the mimetic peptide, at a concentration of 100 μg/mL, were able to decrease the viability of SKOV3, CAOV3, and OVCAR3 cells (p < 0.05). The peptide at this concentration was not able to affect the viability of immortalized non-neoplastic ovarian cells (p > 0.05). ApoA1 decreased SKOV3 cells invasiveness at 300 μg/mL after 72 and 96 h of exposure (p < 0.05), while the ApoA1 mimetic peptide prevented cell invasion at 50 and 100 μg/mL (p < 0.01). Treatment with 100 μg/mL of ApoA1 mimetic peptide decreased Akt phosphorylation in SKOV3 cells (p < 0.01). Accordingly, treatment with increasing concentrations of the peptide sensitized SKOV3, OVCAR3 and CAOV3 cells to cisplatin. This synergistic effect was observed both in vitro and in ovo. Conclusions: These results support the role of ApoA1 and ApoA1 mimetics as suppressors of ovarian tumorigenesis and as chemo-sensitising agents.
Issue Date: 28-Jan-2019
Date of Acceptance: 12-Dec-2018
URI: http://hdl.handle.net/10044/1/70595
DOI: https://doi.org/10.3389/fphar.2018.01524
ISSN: 1663-9812
Publisher: Frontiers Media
Journal / Book Title: Frontiers in Pharmacology
Volume: 9
Copyright Statement: © 2019 Marinho, Lu, Pereira, Monteiro, Gabra and Recchi. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY) (https://creativecommons.org/licenses/by/4.0/). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
Keywords: Science & Technology
Life Sciences & Biomedicine
Pharmacology & Pharmacy
apolipoprotein A1
ApoA1 mimetic peptides
ovarian cancer
platinum sensitization
invasiveness
LYSOPHOSPHATIDIC ACID
APOA-I
EXPRESSION
PROLIFERATION
MEDIATOR
PATHWAY
CELLS
ApoA1 mimetic peptides
apolipoprotein A1
invasiveness
ovarian cancer
platinum sensitization
Science & Technology
Life Sciences & Biomedicine
Pharmacology & Pharmacy
apolipoprotein A1
ApoA1 mimetic peptides
ovarian cancer
platinum sensitization
invasiveness
LYSOPHOSPHATIDIC ACID
APOA-I
EXPRESSION
PROLIFERATION
MEDIATOR
PATHWAY
CELLS
1115 Pharmacology and Pharmaceutical Sciences
Publication Status: Published
Article Number: 1524
Online Publication Date: 2019-01-28
Appears in Collections:Division of Surgery
Division of Cancer



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