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The Effect of Silencing the Genes Responsible for the Level of Sphingosine-1-phosphate on the Apoptosis of Colon Cancer Cells

Sphingosine-1-phosphate (S1P) and ceramides (Cer) are engaged in key events of signal transduction, but their involvement in the pathogenesis of colorectal cancer is not conclusive. The aim of our study was to investigate how the modulation of sphingolipid metabolism through the silencing of the gen...

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Autores principales: Markowski, Adam R., Żbikowski, Arkadiusz, Zabielski, Piotr, Chlabicz, Urszula, Sadowska, Patrycja, Pogodzińska, Karolina, Błachnio-Zabielska, Agnieszka U.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10138425/
https://www.ncbi.nlm.nih.gov/pubmed/37108361
http://dx.doi.org/10.3390/ijms24087197
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author Markowski, Adam R.
Żbikowski, Arkadiusz
Zabielski, Piotr
Chlabicz, Urszula
Sadowska, Patrycja
Pogodzińska, Karolina
Błachnio-Zabielska, Agnieszka U.
author_facet Markowski, Adam R.
Żbikowski, Arkadiusz
Zabielski, Piotr
Chlabicz, Urszula
Sadowska, Patrycja
Pogodzińska, Karolina
Błachnio-Zabielska, Agnieszka U.
author_sort Markowski, Adam R.
collection PubMed
description Sphingosine-1-phosphate (S1P) and ceramides (Cer) are engaged in key events of signal transduction, but their involvement in the pathogenesis of colorectal cancer is not conclusive. The aim of our study was to investigate how the modulation of sphingolipid metabolism through the silencing of the genes involved in the formation (SPHK1) and degradation (SGPL1) of sphingosine-1-phosphate would affect the sphingolipid profile and apoptosis of HCT-116 human colorectal cancer cells. Silencing of SPHK1 expression decreased S1P content in HCT-116 cells, which was accompanied by an elevation in sphingosine, C18:0-Cer, and C18:1-Cer, increase in the expression and activation of Caspase-3 and -9, and augmentation of apoptosis. Interestingly, silencing of SGLP1 expression increased cellular content of both the S1P and Cer (C16:0-; C18:0-; C18:1-; C20:0-; and C22:0-Cer), yet inhibited activation of Caspase-3 and upregulated protein expression of Cathepsin-D. The above findings suggest that modulation of the S1P level and S1P/Cer ratio regulates both cellular apoptosis and CRC metastasis through Cathepsin-D modulation. The cellular ratio of S1P/Cer seems to be a crucial component of the above mechanism.
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spelling pubmed-101384252023-04-28 The Effect of Silencing the Genes Responsible for the Level of Sphingosine-1-phosphate on the Apoptosis of Colon Cancer Cells Markowski, Adam R. Żbikowski, Arkadiusz Zabielski, Piotr Chlabicz, Urszula Sadowska, Patrycja Pogodzińska, Karolina Błachnio-Zabielska, Agnieszka U. Int J Mol Sci Article Sphingosine-1-phosphate (S1P) and ceramides (Cer) are engaged in key events of signal transduction, but their involvement in the pathogenesis of colorectal cancer is not conclusive. The aim of our study was to investigate how the modulation of sphingolipid metabolism through the silencing of the genes involved in the formation (SPHK1) and degradation (SGPL1) of sphingosine-1-phosphate would affect the sphingolipid profile and apoptosis of HCT-116 human colorectal cancer cells. Silencing of SPHK1 expression decreased S1P content in HCT-116 cells, which was accompanied by an elevation in sphingosine, C18:0-Cer, and C18:1-Cer, increase in the expression and activation of Caspase-3 and -9, and augmentation of apoptosis. Interestingly, silencing of SGLP1 expression increased cellular content of both the S1P and Cer (C16:0-; C18:0-; C18:1-; C20:0-; and C22:0-Cer), yet inhibited activation of Caspase-3 and upregulated protein expression of Cathepsin-D. The above findings suggest that modulation of the S1P level and S1P/Cer ratio regulates both cellular apoptosis and CRC metastasis through Cathepsin-D modulation. The cellular ratio of S1P/Cer seems to be a crucial component of the above mechanism. MDPI 2023-04-13 /pmc/articles/PMC10138425/ /pubmed/37108361 http://dx.doi.org/10.3390/ijms24087197 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Markowski, Adam R.
Żbikowski, Arkadiusz
Zabielski, Piotr
Chlabicz, Urszula
Sadowska, Patrycja
Pogodzińska, Karolina
Błachnio-Zabielska, Agnieszka U.
The Effect of Silencing the Genes Responsible for the Level of Sphingosine-1-phosphate on the Apoptosis of Colon Cancer Cells
title The Effect of Silencing the Genes Responsible for the Level of Sphingosine-1-phosphate on the Apoptosis of Colon Cancer Cells
title_full The Effect of Silencing the Genes Responsible for the Level of Sphingosine-1-phosphate on the Apoptosis of Colon Cancer Cells
title_fullStr The Effect of Silencing the Genes Responsible for the Level of Sphingosine-1-phosphate on the Apoptosis of Colon Cancer Cells
title_full_unstemmed The Effect of Silencing the Genes Responsible for the Level of Sphingosine-1-phosphate on the Apoptosis of Colon Cancer Cells
title_short The Effect of Silencing the Genes Responsible for the Level of Sphingosine-1-phosphate on the Apoptosis of Colon Cancer Cells
title_sort effect of silencing the genes responsible for the level of sphingosine-1-phosphate on the apoptosis of colon cancer cells
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10138425/
https://www.ncbi.nlm.nih.gov/pubmed/37108361
http://dx.doi.org/10.3390/ijms24087197
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