Induction of 2-hydroxycatecholestrogens O-methylation: A missing puzzle piece in diagnostics and treatment of lung cancer
Lung cancer is one of the most common cancers worldwide, causing nearly one million deaths each year. Herein, we present the effect of 2-methoxyestradiol (2-ME), the endogenous metabolite of 17β-estradiol (E2), on non-small cell lung cancer (NSCLC) cells. We observed that 2-ME reduced the viability...
| Main Authors: | , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2022-09-01
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| Series: | Redox Biology |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2213231722001677 |
| _version_ | 1811215969795702784 |
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| author | Claudia Musial Narcyz Knap Renata Zaucha Paulina Bastian Giampaolo Barone Giosuè Lo Bosco Fabrizio Lo-Celso Lucyna Konieczna Mariusz Belka Tomasz Bączek Antonella Marino Gammazza Alicja Kuban-Jankowska Francesco Cappello Stephan Nussberger Magdalena Gorska-Ponikowska |
| author_facet | Claudia Musial Narcyz Knap Renata Zaucha Paulina Bastian Giampaolo Barone Giosuè Lo Bosco Fabrizio Lo-Celso Lucyna Konieczna Mariusz Belka Tomasz Bączek Antonella Marino Gammazza Alicja Kuban-Jankowska Francesco Cappello Stephan Nussberger Magdalena Gorska-Ponikowska |
| author_sort | Claudia Musial |
| collection | DOAJ |
| description | Lung cancer is one of the most common cancers worldwide, causing nearly one million deaths each year. Herein, we present the effect of 2-methoxyestradiol (2-ME), the endogenous metabolite of 17β-estradiol (E2), on non-small cell lung cancer (NSCLC) cells. We observed that 2-ME reduced the viability of lung adenocarcinoma in two-dimensional (2D) and three-dimensional (3D) spheroidal A549 cell culture models. Molecular modeling was carried out aiming to visualize amino acid residues within binding pockets of the acyl-protein thioesterases, namely 1 (APT1) and 2 (APT2), and thus to identify which ones were more likely involved in the interaction with 2-ME.Our findings suggest that 2-ME acts as an APT1 inhibitor enhancing protein palmitoylation and oxidative stress phenomena in the lung cancer cell. In order to support our data, metabolomics of blood serum from NSCLC patients was also performed. Moreover, computational analysis suggests that 2-ME as compared to other estrogen metabolism intermediates is relatively safe in terms of its possible non-receptor bioactivity within healthy human cells due to a very low electrophilic potential and hence no substantial risk of spontaneous covalent modification of biologically protective nucleophiles.We propose that 2-ME can be used as a selective tumor biomarker in the course of certain types of lung cancers and possibly as a therapeutic adjuvant or neoadjuvant. |
| first_indexed | 2024-04-12T06:32:17Z |
| format | Article |
| id | doaj.art-499a3a75f7f3413b953812e55fd813a7 |
| institution | Directory Open Access Journal |
| issn | 2213-2317 |
| language | English |
| last_indexed | 2024-04-12T06:32:17Z |
| publishDate | 2022-09-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Redox Biology |
| spelling | doaj.art-499a3a75f7f3413b953812e55fd813a72022-12-22T03:43:59ZengElsevierRedox Biology2213-23172022-09-0155102395Induction of 2-hydroxycatecholestrogens O-methylation: A missing puzzle piece in diagnostics and treatment of lung cancerClaudia Musial0Narcyz Knap1Renata Zaucha2Paulina Bastian3Giampaolo Barone4Giosuè Lo Bosco5Fabrizio Lo-Celso6Lucyna Konieczna7Mariusz Belka8Tomasz Bączek9Antonella Marino Gammazza10Alicja Kuban-Jankowska11Francesco Cappello12Stephan Nussberger13Magdalena Gorska-Ponikowska14Department of Medical Chemistry, Medical University of Gdansk, Debinki 1, 80-211, Gdansk, PolandDepartment of Medical Chemistry, Medical University of Gdansk, Debinki 1, 80-211, Gdansk, PolandDepartment of Clinical Oncology and Radiotherapy, Medical University of Gdansk, 80-214, Gdansk, PolandDepartment of Medical Chemistry, Medical University of Gdansk, Debinki 1, 80-211, Gdansk, PolandDepartment of Biological, Chemical and Pharmaceutical Sciences and Technologies, University of Palermo, 90128, Palermo, ItalyDepartment of Mathematics and Computer Science, University of Palermo, 90133, Palermo, Italy; Euro-Mediterranean Institute of Science and Technology, 90139, Palermo, ItalyDepartment of Physics and Chemistry ‘Emilio Segrè’, University of Palermo, 90128, Palermo, ItalyDepartment of Pharmaceutical Chemistry, Medical University of Gdansk, 80-416, Gdansk, PolandDepartment of Pharmaceutical Chemistry, Medical University of Gdansk, 80-416, Gdansk, PolandDepartment of Pharmaceutical Chemistry, Medical University of Gdansk, 80-416, Gdansk, PolandDepartment of Biomedicine, Neuroscience and Advanced Diagnostics, University of Palermo, 90127, Palermo, ItalyDepartment of Medical Chemistry, Medical University of Gdansk, Debinki 1, 80-211, Gdansk, PolandEuro-Mediterranean Institute of Science and Technology, 90139, Palermo, Italy; Department of Biomedicine, Neuroscience and Advanced Diagnostics, University of Palermo, 90127, Palermo, ItalyDepartment of Biophysics, Institute of Biomaterials and Biomolecular Systems, University of Stuttgart, 70569, Stuttgart, GermanyDepartment of Medical Chemistry, Medical University of Gdansk, Debinki 1, 80-211, Gdansk, Poland; Department of Biological, Chemical and Pharmaceutical Sciences and Technologies, University of Palermo, 90128, Palermo, Italy; Euro-Mediterranean Institute of Science and Technology, 90139, Palermo, Italy; Department of Biophysics, Institute of Biomaterials and Biomolecular Systems, University of Stuttgart, 70569, Stuttgart, Germany; Corresponding author. Department of Medical Chemistry, Medical University of Gdansk, Debinki 1, 80-211, Gdansk, Poland.Lung cancer is one of the most common cancers worldwide, causing nearly one million deaths each year. Herein, we present the effect of 2-methoxyestradiol (2-ME), the endogenous metabolite of 17β-estradiol (E2), on non-small cell lung cancer (NSCLC) cells. We observed that 2-ME reduced the viability of lung adenocarcinoma in two-dimensional (2D) and three-dimensional (3D) spheroidal A549 cell culture models. Molecular modeling was carried out aiming to visualize amino acid residues within binding pockets of the acyl-protein thioesterases, namely 1 (APT1) and 2 (APT2), and thus to identify which ones were more likely involved in the interaction with 2-ME.Our findings suggest that 2-ME acts as an APT1 inhibitor enhancing protein palmitoylation and oxidative stress phenomena in the lung cancer cell. In order to support our data, metabolomics of blood serum from NSCLC patients was also performed. Moreover, computational analysis suggests that 2-ME as compared to other estrogen metabolism intermediates is relatively safe in terms of its possible non-receptor bioactivity within healthy human cells due to a very low electrophilic potential and hence no substantial risk of spontaneous covalent modification of biologically protective nucleophiles.We propose that 2-ME can be used as a selective tumor biomarker in the course of certain types of lung cancers and possibly as a therapeutic adjuvant or neoadjuvant.http://www.sciencedirect.com/science/article/pii/S2213231722001677Lung cancerLung adenocarcinomaNon-small cell lung cancer2-MethoxyestradiolEstrogen metabolitesBiomarker |
| spellingShingle | Claudia Musial Narcyz Knap Renata Zaucha Paulina Bastian Giampaolo Barone Giosuè Lo Bosco Fabrizio Lo-Celso Lucyna Konieczna Mariusz Belka Tomasz Bączek Antonella Marino Gammazza Alicja Kuban-Jankowska Francesco Cappello Stephan Nussberger Magdalena Gorska-Ponikowska Induction of 2-hydroxycatecholestrogens O-methylation: A missing puzzle piece in diagnostics and treatment of lung cancer Redox Biology Lung cancer Lung adenocarcinoma Non-small cell lung cancer 2-Methoxyestradiol Estrogen metabolites Biomarker |
| title | Induction of 2-hydroxycatecholestrogens O-methylation: A missing puzzle piece in diagnostics and treatment of lung cancer |
| title_full | Induction of 2-hydroxycatecholestrogens O-methylation: A missing puzzle piece in diagnostics and treatment of lung cancer |
| title_fullStr | Induction of 2-hydroxycatecholestrogens O-methylation: A missing puzzle piece in diagnostics and treatment of lung cancer |
| title_full_unstemmed | Induction of 2-hydroxycatecholestrogens O-methylation: A missing puzzle piece in diagnostics and treatment of lung cancer |
| title_short | Induction of 2-hydroxycatecholestrogens O-methylation: A missing puzzle piece in diagnostics and treatment of lung cancer |
| title_sort | induction of 2 hydroxycatecholestrogens o methylation a missing puzzle piece in diagnostics and treatment of lung cancer |
| topic | Lung cancer Lung adenocarcinoma Non-small cell lung cancer 2-Methoxyestradiol Estrogen metabolites Biomarker |
| url | http://www.sciencedirect.com/science/article/pii/S2213231722001677 |
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