Five‐to‐Seven Carbon Glycols Severely Impair Bioenergetics and Metabolism of Aggressive Lung Cancer Cells
Lung cancer is the leading cause of cancer deaths. Nonsmall cell lung cancer (NSCLC) accounts for the vast majority of the histological subtypes and at advanced stage exhibits extremely low survival rate. Certain compounds, such as glycols, inhibit migration and decreased viability of the highly met...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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Wiley-VCH
2022-09-01
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| Series: | Advanced NanoBiomed Research |
| Subjects: | |
| Online Access: | https://doi.org/10.1002/anbr.202200050 |
| _version_ | 1828113457494360064 |
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| author | Sílvio Terra Stefanello Caren Rigon Mizdal Ihab Azzam Lilly Döhlinger Andrea Oeckinghaus Victor Shahin |
| author_facet | Sílvio Terra Stefanello Caren Rigon Mizdal Ihab Azzam Lilly Döhlinger Andrea Oeckinghaus Victor Shahin |
| author_sort | Sílvio Terra Stefanello |
| collection | DOAJ |
| description | Lung cancer is the leading cause of cancer deaths. Nonsmall cell lung cancer (NSCLC) accounts for the vast majority of the histological subtypes and at advanced stage exhibits extremely low survival rate. Certain compounds, such as glycols, inhibit migration and decreased viability of the highly metastatic NSCLC cells A549_3R has been recently shown. The glycols‐induced effects are associated with a parallel reduction of ATP production, detected in A549_3R spheroids embedded in 3D desmoplastic‐like extracellular matrix, following overnight treatment. Herein, selected glycols are tested for their ability to acutely compromise bioenergetics, metabolism, and viability of A549_3R cells. Therefore, 1,5‐pentanediol (1,5‐PD), 1,6‐hexanediol (1,6‐HD), and 1,7‐heptanediol (1,7‐Hept) turn out to be the most effective. They interfere with key enzymes in glycolysis and elicit most or all of the following responses: acute collapse of the critical mitochondrial membrane potential, substantial reduction of ATP, pyruvate and L‐lactate levels, and massive increase in reactive oxygen species production. Moreover, computational docking analysis reveals that the glycols bind to the substrate‐binding residues of lactate dehydrogenase A, which catalyzes the interconversion of pyruvate and lactate and is upregulated in aggressive tumors. Hence, the effective glycols may be promising anticancer compounds, or lead substances, for localized and intratumoral applications. |
| first_indexed | 2024-04-11T12:07:30Z |
| format | Article |
| id | doaj.art-6bca76d1634f4a17aa200aab2c0a9ca8 |
| institution | Directory Open Access Journal |
| issn | 2699-9307 |
| language | English |
| last_indexed | 2024-04-11T12:07:30Z |
| publishDate | 2022-09-01 |
| publisher | Wiley-VCH |
| record_format | Article |
| series | Advanced NanoBiomed Research |
| spelling | doaj.art-6bca76d1634f4a17aa200aab2c0a9ca82022-12-22T04:24:42ZengWiley-VCHAdvanced NanoBiomed Research2699-93072022-09-0129n/an/a10.1002/anbr.202200050Five‐to‐Seven Carbon Glycols Severely Impair Bioenergetics and Metabolism of Aggressive Lung Cancer CellsSílvio Terra Stefanello0Caren Rigon Mizdal1Ihab Azzam2Lilly Döhlinger3Andrea Oeckinghaus4Victor Shahin5Institute of Physiology II University of Münster Robert-Koch-Str. 27b 48149 Münster GermanyInstitute of Physiology II University of Münster Robert-Koch-Str. 27b 48149 Münster GermanyInstitute of Immunology University of Münster Röntgen-Str. 21 48149 Münster GermanyInstitute of Physiology II University of Münster Robert-Koch-Str. 27b 48149 Münster GermanyInstitute of Molecular Tumor Biology University of Münster Robert-Koch-Str. 43 48149 Münster GermanyInstitute of Physiology II University of Münster Robert-Koch-Str. 27b 48149 Münster GermanyLung cancer is the leading cause of cancer deaths. Nonsmall cell lung cancer (NSCLC) accounts for the vast majority of the histological subtypes and at advanced stage exhibits extremely low survival rate. Certain compounds, such as glycols, inhibit migration and decreased viability of the highly metastatic NSCLC cells A549_3R has been recently shown. The glycols‐induced effects are associated with a parallel reduction of ATP production, detected in A549_3R spheroids embedded in 3D desmoplastic‐like extracellular matrix, following overnight treatment. Herein, selected glycols are tested for their ability to acutely compromise bioenergetics, metabolism, and viability of A549_3R cells. Therefore, 1,5‐pentanediol (1,5‐PD), 1,6‐hexanediol (1,6‐HD), and 1,7‐heptanediol (1,7‐Hept) turn out to be the most effective. They interfere with key enzymes in glycolysis and elicit most or all of the following responses: acute collapse of the critical mitochondrial membrane potential, substantial reduction of ATP, pyruvate and L‐lactate levels, and massive increase in reactive oxygen species production. Moreover, computational docking analysis reveals that the glycols bind to the substrate‐binding residues of lactate dehydrogenase A, which catalyzes the interconversion of pyruvate and lactate and is upregulated in aggressive tumors. Hence, the effective glycols may be promising anticancer compounds, or lead substances, for localized and intratumoral applications.https://doi.org/10.1002/anbr.202200050bioenergeticscellular physiologylactate dehydrogenase Alung cancermitochondria |
| spellingShingle | Sílvio Terra Stefanello Caren Rigon Mizdal Ihab Azzam Lilly Döhlinger Andrea Oeckinghaus Victor Shahin Five‐to‐Seven Carbon Glycols Severely Impair Bioenergetics and Metabolism of Aggressive Lung Cancer Cells Advanced NanoBiomed Research bioenergetics cellular physiology lactate dehydrogenase A lung cancer mitochondria |
| title | Five‐to‐Seven Carbon Glycols Severely Impair Bioenergetics and Metabolism of Aggressive Lung Cancer Cells |
| title_full | Five‐to‐Seven Carbon Glycols Severely Impair Bioenergetics and Metabolism of Aggressive Lung Cancer Cells |
| title_fullStr | Five‐to‐Seven Carbon Glycols Severely Impair Bioenergetics and Metabolism of Aggressive Lung Cancer Cells |
| title_full_unstemmed | Five‐to‐Seven Carbon Glycols Severely Impair Bioenergetics and Metabolism of Aggressive Lung Cancer Cells |
| title_short | Five‐to‐Seven Carbon Glycols Severely Impair Bioenergetics and Metabolism of Aggressive Lung Cancer Cells |
| title_sort | five to seven carbon glycols severely impair bioenergetics and metabolism of aggressive lung cancer cells |
| topic | bioenergetics cellular physiology lactate dehydrogenase A lung cancer mitochondria |
| url | https://doi.org/10.1002/anbr.202200050 |
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