20-Hydroxyecdysone Confers Antioxidant and Antineoplastic Properties in Human Non-Small Cell Lung Cancer Cells
Shuvalov O. Kirdeeva Y. Fefilova E. Netsvetay S. Zorin M. Vlasova Y. Fedorova O. Daks A. Parfenyev S. Barlev N.
May 2023MDPI
Metabolites
2023#13Issue 5
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.
20-hydroxyecdysone , anticancer therapy , cancer stem cells (CSCs) , energy metabolism , glycolysis , metabolic inhibitors , non-small cell lung cancer , one-carbon metabolism , respiration
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Institute of Cytology, Russian Academy of Sciences, St. Petersburg, 194064, Russian Federation
Almazov National Medical Research Center Russia, St. Petersburg, 197341, Russian Federation
School of Medicine, Nazarbayev University, Astana, 001000, Kazakhstan
Institute of Fundamental Medicine and Biology, Kazan Federal University, Kazan, 420008, Russian Federation
Institute of Cytology
Almazov National Medical Research Center Russia
School of Medicine
Institute of Fundamental Medicine and Biology
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