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Proline-Dependent Induction of Apoptosis in Oral Squamous Cell Carcinoma (OSCC)—The Effect of Celecoxib
Background: Oral squamous cell carcinoma remains a significant worldwide public health challenge, associated with high morbidity and mortality. Treatment of this type of cancer lacks effective medication. Moreover, there are very few specific biomarkers that are useful in early diagnosis or treatmen...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7016823/ https://www.ncbi.nlm.nih.gov/pubmed/31935820 http://dx.doi.org/10.3390/cancers12010136 |
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author | Tołoczko-Iwaniuk, Natalia Dziemiańczyk-Pakieła, Dorota Celińska-Janowicz, Katarzyna Zaręba, Ilona Klupczyńska, Agnieszka Kokot, Zenon J. Nowaszewska, Beata Klaudia Reszeć, Joanna Borys, Jan Miltyk, Wojciech |
author_facet | Tołoczko-Iwaniuk, Natalia Dziemiańczyk-Pakieła, Dorota Celińska-Janowicz, Katarzyna Zaręba, Ilona Klupczyńska, Agnieszka Kokot, Zenon J. Nowaszewska, Beata Klaudia Reszeć, Joanna Borys, Jan Miltyk, Wojciech |
author_sort | Tołoczko-Iwaniuk, Natalia |
collection | PubMed |
description | Background: Oral squamous cell carcinoma remains a significant worldwide public health challenge, associated with high morbidity and mortality. Treatment of this type of cancer lacks effective medication. Moreover, there are very few specific biomarkers that are useful in early diagnosis or treatment optimisation. Proline metabolism may prove to be of importance in the search for new treatment modalities. Methods: To evaluate the significance of proline metabolism in the development of oral cancer, proline concentration was assessed in oral cancer tissue and normal oral mucosa. The results were compared to the clinical stage and histological grade of the tumours. Moreover, the expression of proteins involved in proline metabolism via proline dehydrogenase/oxidase (PRODH/POX, PPARγ, HIF1-α) was determined. In the next stage of the study, conducted on cell lines of tongue cancer treated with celecoxib, the aforementioned factors involved in proline metabolism were evaluated. Cellular viability and cell proliferation, as well as apoptosis, were also assessed. Results: Our research results indicate that a high intracellular proline concentration and expression of factors involved in its metabolism correlate with the clinical stage and histological grade of oral cancer. Moreover, we are the first researchers to demonstrate that celecoxib can affect proline metabolism, causing an increase in pro-apoptotic factors (PRODH/POX, PPARγ), reducing the expression of HIF-1α and activating apoptosis. Conclusions: Proline metabolism, due to its involvement in the process of apoptosis, can be of great importance in anticancer therapy. It appears that celecoxib, which influences the PRODH/POX pathway, may be a promising therapeutic compound in oral cancer treatment. |
format | Online Article Text |
id | pubmed-7016823 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-70168232020-02-28 Proline-Dependent Induction of Apoptosis in Oral Squamous Cell Carcinoma (OSCC)—The Effect of Celecoxib Tołoczko-Iwaniuk, Natalia Dziemiańczyk-Pakieła, Dorota Celińska-Janowicz, Katarzyna Zaręba, Ilona Klupczyńska, Agnieszka Kokot, Zenon J. Nowaszewska, Beata Klaudia Reszeć, Joanna Borys, Jan Miltyk, Wojciech Cancers (Basel) Article Background: Oral squamous cell carcinoma remains a significant worldwide public health challenge, associated with high morbidity and mortality. Treatment of this type of cancer lacks effective medication. Moreover, there are very few specific biomarkers that are useful in early diagnosis or treatment optimisation. Proline metabolism may prove to be of importance in the search for new treatment modalities. Methods: To evaluate the significance of proline metabolism in the development of oral cancer, proline concentration was assessed in oral cancer tissue and normal oral mucosa. The results were compared to the clinical stage and histological grade of the tumours. Moreover, the expression of proteins involved in proline metabolism via proline dehydrogenase/oxidase (PRODH/POX, PPARγ, HIF1-α) was determined. In the next stage of the study, conducted on cell lines of tongue cancer treated with celecoxib, the aforementioned factors involved in proline metabolism were evaluated. Cellular viability and cell proliferation, as well as apoptosis, were also assessed. Results: Our research results indicate that a high intracellular proline concentration and expression of factors involved in its metabolism correlate with the clinical stage and histological grade of oral cancer. Moreover, we are the first researchers to demonstrate that celecoxib can affect proline metabolism, causing an increase in pro-apoptotic factors (PRODH/POX, PPARγ), reducing the expression of HIF-1α and activating apoptosis. Conclusions: Proline metabolism, due to its involvement in the process of apoptosis, can be of great importance in anticancer therapy. It appears that celecoxib, which influences the PRODH/POX pathway, may be a promising therapeutic compound in oral cancer treatment. MDPI 2020-01-06 /pmc/articles/PMC7016823/ /pubmed/31935820 http://dx.doi.org/10.3390/cancers12010136 Text en © 2020 by the authors. 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 (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Tołoczko-Iwaniuk, Natalia Dziemiańczyk-Pakieła, Dorota Celińska-Janowicz, Katarzyna Zaręba, Ilona Klupczyńska, Agnieszka Kokot, Zenon J. Nowaszewska, Beata Klaudia Reszeć, Joanna Borys, Jan Miltyk, Wojciech Proline-Dependent Induction of Apoptosis in Oral Squamous Cell Carcinoma (OSCC)—The Effect of Celecoxib |
title | Proline-Dependent Induction of Apoptosis in Oral Squamous Cell Carcinoma (OSCC)—The Effect of Celecoxib |
title_full | Proline-Dependent Induction of Apoptosis in Oral Squamous Cell Carcinoma (OSCC)—The Effect of Celecoxib |
title_fullStr | Proline-Dependent Induction of Apoptosis in Oral Squamous Cell Carcinoma (OSCC)—The Effect of Celecoxib |
title_full_unstemmed | Proline-Dependent Induction of Apoptosis in Oral Squamous Cell Carcinoma (OSCC)—The Effect of Celecoxib |
title_short | Proline-Dependent Induction of Apoptosis in Oral Squamous Cell Carcinoma (OSCC)—The Effect of Celecoxib |
title_sort | proline-dependent induction of apoptosis in oral squamous cell carcinoma (oscc)—the effect of celecoxib |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7016823/ https://www.ncbi.nlm.nih.gov/pubmed/31935820 http://dx.doi.org/10.3390/cancers12010136 |
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