Mucin 1 as a Molecular Target of a Novel Diisoquinoline Derivative Combined with Anti-MUC1 Antibody in AGS Gastric Cancer Cells

Background: The aim of the study was to examine the molecular mechanism of the anticancer action of a monoclonal antibody against MUC1 and a diisoquinoline derivative (OM-86II) in human gastric cancer cells. Methods: The cell viability was measured by the MTT assay. The disruption of mitochondrial m...

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Autores principales:	Agnieszka Gornowicz, Wojciech Szymanowski, Krzysztof Bielawski, Zbigniew Kałuża, Olga Michalak, Anna Bielawska
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	MUC1 diisoquinoline derivative apoptosis autophagy gastric cancer Organic chemistry QD241-441
Acceso en línea:	https://doaj.org/article/a35114e8c455458b942e5441cc4be2a7
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spelling	oai:doaj.org-article:a35114e8c455458b942e5441cc4be2a72021-11-11T18:30:09ZMucin 1 as a Molecular Target of a Novel Diisoquinoline Derivative Combined with Anti-MUC1 Antibody in AGS Gastric Cancer Cells10.3390/molecules262165041420-3049https://doaj.org/article/a35114e8c455458b942e5441cc4be2a72021-10-01T00:00:00Zhttps://www.mdpi.com/1420-3049/26/21/6504https://doaj.org/toc/1420-3049Background: The aim of the study was to examine the molecular mechanism of the anticancer action of a monoclonal antibody against MUC1 and a diisoquinoline derivative (OM-86II) in human gastric cancer cells. Methods: The cell viability was measured by the MTT assay. The disruption of mitochondrial membrane potential and activity of caspase-8 and caspase-9 was performed by flow cytometry. Fluorescent microscopy was used to confirm the proapoptotic effect of compounds. LC3A, LC3B and Beclin-1 concentrations were analyzed to check the influence of the compounds on induction of autophagy. ELISA assessments were performed to measure the concentration of mTOR, sICAM1, MMP-2, MMP-9 and pro-apoptotic Bax. Results: The anti-MUC1 antibody with the diisoquinoline derivative (OM-86II) significantly reduced gastric cancer cells’ viability. This was accompanied by an increase in caspase-8 and caspase-9 activity as well as high concentrations of pro-apoptotic Bax. We also proved that the anti-MUC1 antibody with OM-86II decreased the concentrations of MMP-9, sICAM1 and mTOR in gastric cancer cells. After 48 h of incubation with such a combination, we observed higher levels of the crucial component of autophagosomes (LC3) and Beclin-1. Conclusions: Our study proved that the anti-MUC1 antibody sensitizes human gastric cancer cells to the novel diisoquinoline derivative (OM-86II) via induction of apoptosis and autophagy, and inhibition of selected proteins such as mTOR, sICAM1 and MMP-9.Agnieszka GornowiczWojciech SzymanowskiKrzysztof BielawskiZbigniew KałużaOlga MichalakAnna BielawskaMDPI AGarticleMUC1diisoquinoline derivativeapoptosisautophagygastric cancerOrganic chemistryQD241-441ENMolecules, Vol 26, Iss 6504, p 6504 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	MUC1 diisoquinoline derivative apoptosis autophagy gastric cancer Organic chemistry QD241-441
spellingShingle	MUC1 diisoquinoline derivative apoptosis autophagy gastric cancer Organic chemistry QD241-441 Agnieszka Gornowicz Wojciech Szymanowski Krzysztof Bielawski Zbigniew Kałuża Olga Michalak Anna Bielawska Mucin 1 as a Molecular Target of a Novel Diisoquinoline Derivative Combined with Anti-MUC1 Antibody in AGS Gastric Cancer Cells
description	Background: The aim of the study was to examine the molecular mechanism of the anticancer action of a monoclonal antibody against MUC1 and a diisoquinoline derivative (OM-86II) in human gastric cancer cells. Methods: The cell viability was measured by the MTT assay. The disruption of mitochondrial membrane potential and activity of caspase-8 and caspase-9 was performed by flow cytometry. Fluorescent microscopy was used to confirm the proapoptotic effect of compounds. LC3A, LC3B and Beclin-1 concentrations were analyzed to check the influence of the compounds on induction of autophagy. ELISA assessments were performed to measure the concentration of mTOR, sICAM1, MMP-2, MMP-9 and pro-apoptotic Bax. Results: The anti-MUC1 antibody with the diisoquinoline derivative (OM-86II) significantly reduced gastric cancer cells’ viability. This was accompanied by an increase in caspase-8 and caspase-9 activity as well as high concentrations of pro-apoptotic Bax. We also proved that the anti-MUC1 antibody with OM-86II decreased the concentrations of MMP-9, sICAM1 and mTOR in gastric cancer cells. After 48 h of incubation with such a combination, we observed higher levels of the crucial component of autophagosomes (LC3) and Beclin-1. Conclusions: Our study proved that the anti-MUC1 antibody sensitizes human gastric cancer cells to the novel diisoquinoline derivative (OM-86II) via induction of apoptosis and autophagy, and inhibition of selected proteins such as mTOR, sICAM1 and MMP-9.
format	article
author	Agnieszka Gornowicz Wojciech Szymanowski Krzysztof Bielawski Zbigniew Kałuża Olga Michalak Anna Bielawska
author_facet	Agnieszka Gornowicz Wojciech Szymanowski Krzysztof Bielawski Zbigniew Kałuża Olga Michalak Anna Bielawska
author_sort	Agnieszka Gornowicz
title	Mucin 1 as a Molecular Target of a Novel Diisoquinoline Derivative Combined with Anti-MUC1 Antibody in AGS Gastric Cancer Cells
title_short	Mucin 1 as a Molecular Target of a Novel Diisoquinoline Derivative Combined with Anti-MUC1 Antibody in AGS Gastric Cancer Cells
title_full	Mucin 1 as a Molecular Target of a Novel Diisoquinoline Derivative Combined with Anti-MUC1 Antibody in AGS Gastric Cancer Cells
title_fullStr	Mucin 1 as a Molecular Target of a Novel Diisoquinoline Derivative Combined with Anti-MUC1 Antibody in AGS Gastric Cancer Cells
title_full_unstemmed	Mucin 1 as a Molecular Target of a Novel Diisoquinoline Derivative Combined with Anti-MUC1 Antibody in AGS Gastric Cancer Cells
title_sort	mucin 1 as a molecular target of a novel diisoquinoline derivative combined with anti-muc1 antibody in ags gastric cancer cells
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/a35114e8c455458b942e5441cc4be2a7
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Mucin 1 as a Molecular Target of a Novel Diisoquinoline Derivative Combined with Anti-MUC1 Antibody in AGS Gastric Cancer Cells

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