20-Hydroxyecdysone Confers Antioxidant and Antineoplastic Properties in Human Non-Small Cell Lung Cancer Cells

20-Hydroxyecdysone (20E) is an arthropod hormone which is synthesized by some plants as part of their defense mechanism. In humans, 20E has no hormonal activity but possesses a number of beneficial pharmacological properties including anabolic, adaptogenic, hypoglycemic, and antioxidant properties,...

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Main Authors: Oleg Shuvalov, Yulia Kirdeeva, Elizaveta Fefilova, Sofia Netsvetay, Mark Zorin, Yulia Vlasova, Olga Fedorova, Alexandra Daks, Sergey Parfenyev, Nickolai Barlev
Format: Article
Language:English
Published: MDPI AG 2023-05-01
Series:Metabolites
Subjects:
Online Access:https://www.mdpi.com/2218-1989/13/5/656
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author Oleg Shuvalov
Yulia Kirdeeva
Elizaveta Fefilova
Sofia Netsvetay
Mark Zorin
Yulia Vlasova
Olga Fedorova
Alexandra Daks
Sergey Parfenyev
Nickolai Barlev
author_facet Oleg Shuvalov
Yulia Kirdeeva
Elizaveta Fefilova
Sofia Netsvetay
Mark Zorin
Yulia Vlasova
Olga Fedorova
Alexandra Daks
Sergey Parfenyev
Nickolai Barlev
author_sort Oleg Shuvalov
collection DOAJ
description 20-Hydroxyecdysone (20E) is an arthropod hormone which is synthesized by some plants as part of their defense mechanism. In humans, 20E has no hormonal activity but possesses a number of beneficial pharmacological properties including anabolic, adaptogenic, hypoglycemic, and antioxidant properties, as well as cardio-, hepato-, and neuroprotective features. Recent studies have shown that 20E may also possess antineoplastic activity. In the present study, we reveal the anticancer properties of 20E in Non-Small Cell Lung Cancer (NSCLC) cell lines. 20E displayed significant antioxidant capacities and induced the expression of antioxidative stress response genes. The RNA-seq analysis of 20E-treated lung cancer cells revealed the attenuation of genes involved in different metabolic processes. Indeed, 20E suppressed several enzymes of glycolysis and one-carbon metabolism, as well as their key transcriptional regulators—c-Myc and ATF4, respectively. Accordingly, using the SeaHorse energy profiling approach, we observed the inhibition of glycolysis and respiration mediated by 20E treatment. Furthermore, 20E sensibilized lung cancer cells to metabolic inhibitors and markedly suppressed the expression of Cancer Stem Cells (CSCs) markers. Thus, in addition to the known beneficial pharmacological activities of 20E, our data uncovered novel antineoplastic properties of 20E in NSCLC cells.
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spelling doaj.art-ecbd015095914a1f95105465f923e5fc2023-11-18T02:26:00ZengMDPI AGMetabolites2218-19892023-05-0113565610.3390/metabo1305065620-Hydroxyecdysone Confers Antioxidant and Antineoplastic Properties in Human Non-Small Cell Lung Cancer CellsOleg Shuvalov0Yulia Kirdeeva1Elizaveta Fefilova2Sofia Netsvetay3Mark Zorin4Yulia Vlasova5Olga Fedorova6Alexandra Daks7Sergey Parfenyev8Nickolai Barlev9Institute of Cytology, Russian Academy of Sciences, 194064 St. Petersburg, RussiaInstitute of Cytology, Russian Academy of Sciences, 194064 St. Petersburg, RussiaInstitute of Cytology, Russian Academy of Sciences, 194064 St. Petersburg, RussiaInstitute of Cytology, Russian Academy of Sciences, 194064 St. Petersburg, RussiaInstitute of Cytology, Russian Academy of Sciences, 194064 St. Petersburg, RussiaAlmazov National Medical Research Center Russia, 197341 St. Petersburg, RussiaInstitute of Cytology, Russian Academy of Sciences, 194064 St. Petersburg, RussiaInstitute of Cytology, Russian Academy of Sciences, 194064 St. Petersburg, RussiaInstitute of Cytology, Russian Academy of Sciences, 194064 St. Petersburg, RussiaInstitute of Cytology, Russian Academy of Sciences, 194064 St. Petersburg, Russia20-Hydroxyecdysone (20E) is an arthropod hormone which is synthesized by some plants as part of their defense mechanism. In humans, 20E has no hormonal activity but possesses a number of beneficial pharmacological properties including anabolic, adaptogenic, hypoglycemic, and antioxidant properties, as well as cardio-, hepato-, and neuroprotective features. Recent studies have shown that 20E may also possess antineoplastic activity. In the present study, we reveal the anticancer properties of 20E in Non-Small Cell Lung Cancer (NSCLC) cell lines. 20E displayed significant antioxidant capacities and induced the expression of antioxidative stress response genes. The RNA-seq analysis of 20E-treated lung cancer cells revealed the attenuation of genes involved in different metabolic processes. Indeed, 20E suppressed several enzymes of glycolysis and one-carbon metabolism, as well as their key transcriptional regulators—c-Myc and ATF4, respectively. Accordingly, using the SeaHorse energy profiling approach, we observed the inhibition of glycolysis and respiration mediated by 20E treatment. Furthermore, 20E sensibilized lung cancer cells to metabolic inhibitors and markedly suppressed the expression of Cancer Stem Cells (CSCs) markers. Thus, in addition to the known beneficial pharmacological activities of 20E, our data uncovered novel antineoplastic properties of 20E in NSCLC cells.https://www.mdpi.com/2218-1989/13/5/65620-hydroxyecdysonenon-small cell lung cancerglycolysisrespirationenergy metabolismone-carbon metabolism
spellingShingle Oleg Shuvalov
Yulia Kirdeeva
Elizaveta Fefilova
Sofia Netsvetay
Mark Zorin
Yulia Vlasova
Olga Fedorova
Alexandra Daks
Sergey Parfenyev
Nickolai Barlev
20-Hydroxyecdysone Confers Antioxidant and Antineoplastic Properties in Human Non-Small Cell Lung Cancer Cells
Metabolites
20-hydroxyecdysone
non-small cell lung cancer
glycolysis
respiration
energy metabolism
one-carbon metabolism
title 20-Hydroxyecdysone Confers Antioxidant and Antineoplastic Properties in Human Non-Small Cell Lung Cancer Cells
title_full 20-Hydroxyecdysone Confers Antioxidant and Antineoplastic Properties in Human Non-Small Cell Lung Cancer Cells
title_fullStr 20-Hydroxyecdysone Confers Antioxidant and Antineoplastic Properties in Human Non-Small Cell Lung Cancer Cells
title_full_unstemmed 20-Hydroxyecdysone Confers Antioxidant and Antineoplastic Properties in Human Non-Small Cell Lung Cancer Cells
title_short 20-Hydroxyecdysone Confers Antioxidant and Antineoplastic Properties in Human Non-Small Cell Lung Cancer Cells
title_sort 20 hydroxyecdysone confers antioxidant and antineoplastic properties in human non small cell lung cancer cells
topic 20-hydroxyecdysone
non-small cell lung cancer
glycolysis
respiration
energy metabolism
one-carbon metabolism
url https://www.mdpi.com/2218-1989/13/5/656
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