Cargando…
Bardoxolone-Methyl (CDDO-Me) Impairs Tumor Growth and Induces Radiosensitization of Oral Squamous Cell Carcinoma Cells
Radiotherapy represents a common treatment strategy for patients suffering from oral squamous cell carcinoma (OSCC). However, application of radiotherapy is immanently limited by radio-sensitivity of normal tissue surrounding the tumor sites. In this study, we used normal human epithelial keratinocy...
Autores principales: | , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2021
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7878525/ https://www.ncbi.nlm.nih.gov/pubmed/33584286 http://dx.doi.org/10.3389/fphar.2020.607580 |
_version_ | 1783650353190797312 |
---|---|
author | Hermann, Cornelius Lang, Simon Popp, Tanja Hafner, Susanne Steinritz, Dirk Rump, Alexis Port, Matthias Eder, Stefan |
author_facet | Hermann, Cornelius Lang, Simon Popp, Tanja Hafner, Susanne Steinritz, Dirk Rump, Alexis Port, Matthias Eder, Stefan |
author_sort | Hermann, Cornelius |
collection | PubMed |
description | Radiotherapy represents a common treatment strategy for patients suffering from oral squamous cell carcinoma (OSCC). However, application of radiotherapy is immanently limited by radio-sensitivity of normal tissue surrounding the tumor sites. In this study, we used normal human epithelial keratinocytes (NHEK) and OSCC cells (Cal-27) as models to investigate radio-modulating and anti-tumor effects of the synthetic triterpenoid 2-cyano-3,12-dioxooleana-1,9,-dien-28-oic acid methyl ester (CDDO-Me). Nanomolar CDDO-Me significantly reduced OSCC tumor xenograft-growth in-ovo applying the chick chorioallantoic membrane (CAM) assay. In the presence of CDDO-Me reactive oxygen species (ROS) were found to be reduced in NHEK when applying radiation doses of 8 Gy, whereas ROS levels in OSCC cells rose significantly even without radiation. In parallel, CDDO-Me was shown to enhance metabolic activity in malignant cells only as indicated by significant accumulation of reducing equivalents NADPH/NADH. Furthermore, antioxidative heme oxygenase-1 (HO-1) levels were only enhanced in NHEK and not in the OSCC cell line, as shown by immunoblotting. Clonogenic survival was left unchanged by CDDO-Me treatment in NHEK but revealed to be abolished almost completely in OSCC cells. Our results indicate anti-cancer and radio-sensitizing effects of CDDO-Me treatment in OSCC cells, whereas nanomolar CDDO-Me failed to provoke clear detrimental consequences in non-malignant keratinocytes. We conclude, that the observed differential aftermath of CDDO-Me treatment in malignant OSCC and non-malignant skin cells may be utilized to broaden the therapeutic range of clinical radiotherapy. |
format | Online Article Text |
id | pubmed-7878525 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-78785252021-02-13 Bardoxolone-Methyl (CDDO-Me) Impairs Tumor Growth and Induces Radiosensitization of Oral Squamous Cell Carcinoma Cells Hermann, Cornelius Lang, Simon Popp, Tanja Hafner, Susanne Steinritz, Dirk Rump, Alexis Port, Matthias Eder, Stefan Front Pharmacol Pharmacology Radiotherapy represents a common treatment strategy for patients suffering from oral squamous cell carcinoma (OSCC). However, application of radiotherapy is immanently limited by radio-sensitivity of normal tissue surrounding the tumor sites. In this study, we used normal human epithelial keratinocytes (NHEK) and OSCC cells (Cal-27) as models to investigate radio-modulating and anti-tumor effects of the synthetic triterpenoid 2-cyano-3,12-dioxooleana-1,9,-dien-28-oic acid methyl ester (CDDO-Me). Nanomolar CDDO-Me significantly reduced OSCC tumor xenograft-growth in-ovo applying the chick chorioallantoic membrane (CAM) assay. In the presence of CDDO-Me reactive oxygen species (ROS) were found to be reduced in NHEK when applying radiation doses of 8 Gy, whereas ROS levels in OSCC cells rose significantly even without radiation. In parallel, CDDO-Me was shown to enhance metabolic activity in malignant cells only as indicated by significant accumulation of reducing equivalents NADPH/NADH. Furthermore, antioxidative heme oxygenase-1 (HO-1) levels were only enhanced in NHEK and not in the OSCC cell line, as shown by immunoblotting. Clonogenic survival was left unchanged by CDDO-Me treatment in NHEK but revealed to be abolished almost completely in OSCC cells. Our results indicate anti-cancer and radio-sensitizing effects of CDDO-Me treatment in OSCC cells, whereas nanomolar CDDO-Me failed to provoke clear detrimental consequences in non-malignant keratinocytes. We conclude, that the observed differential aftermath of CDDO-Me treatment in malignant OSCC and non-malignant skin cells may be utilized to broaden the therapeutic range of clinical radiotherapy. Frontiers Media S.A. 2021-01-29 /pmc/articles/PMC7878525/ /pubmed/33584286 http://dx.doi.org/10.3389/fphar.2020.607580 Text en Copyright © 2021 Hermann, Lang, Popp, Hafner, Steinritz, Rump, Port and Eder. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY) (http://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. |
spellingShingle | Pharmacology Hermann, Cornelius Lang, Simon Popp, Tanja Hafner, Susanne Steinritz, Dirk Rump, Alexis Port, Matthias Eder, Stefan Bardoxolone-Methyl (CDDO-Me) Impairs Tumor Growth and Induces Radiosensitization of Oral Squamous Cell Carcinoma Cells |
title | Bardoxolone-Methyl (CDDO-Me) Impairs Tumor Growth and Induces Radiosensitization of Oral Squamous Cell Carcinoma Cells |
title_full | Bardoxolone-Methyl (CDDO-Me) Impairs Tumor Growth and Induces Radiosensitization of Oral Squamous Cell Carcinoma Cells |
title_fullStr | Bardoxolone-Methyl (CDDO-Me) Impairs Tumor Growth and Induces Radiosensitization of Oral Squamous Cell Carcinoma Cells |
title_full_unstemmed | Bardoxolone-Methyl (CDDO-Me) Impairs Tumor Growth and Induces Radiosensitization of Oral Squamous Cell Carcinoma Cells |
title_short | Bardoxolone-Methyl (CDDO-Me) Impairs Tumor Growth and Induces Radiosensitization of Oral Squamous Cell Carcinoma Cells |
title_sort | bardoxolone-methyl (cddo-me) impairs tumor growth and induces radiosensitization of oral squamous cell carcinoma cells |
topic | Pharmacology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7878525/ https://www.ncbi.nlm.nih.gov/pubmed/33584286 http://dx.doi.org/10.3389/fphar.2020.607580 |
work_keys_str_mv | AT hermanncornelius bardoxolonemethylcddomeimpairstumorgrowthandinducesradiosensitizationoforalsquamouscellcarcinomacells AT langsimon bardoxolonemethylcddomeimpairstumorgrowthandinducesradiosensitizationoforalsquamouscellcarcinomacells AT popptanja bardoxolonemethylcddomeimpairstumorgrowthandinducesradiosensitizationoforalsquamouscellcarcinomacells AT hafnersusanne bardoxolonemethylcddomeimpairstumorgrowthandinducesradiosensitizationoforalsquamouscellcarcinomacells AT steinritzdirk bardoxolonemethylcddomeimpairstumorgrowthandinducesradiosensitizationoforalsquamouscellcarcinomacells AT rumpalexis bardoxolonemethylcddomeimpairstumorgrowthandinducesradiosensitizationoforalsquamouscellcarcinomacells AT portmatthias bardoxolonemethylcddomeimpairstumorgrowthandinducesradiosensitizationoforalsquamouscellcarcinomacells AT ederstefan bardoxolonemethylcddomeimpairstumorgrowthandinducesradiosensitizationoforalsquamouscellcarcinomacells |