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

Author:

Shuvalov Oleg1ORCID,Kirdeeva Yulia1ORCID,Fefilova Elizaveta1,Netsvetay Sofia1,Zorin Mark1,Vlasova Yulia2,Fedorova Olga1,Daks Alexandra1ORCID,Parfenyev Sergey1,Barlev Nickolai134

Affiliation:

1. Institute of Cytology, Russian Academy of Sciences, 194064 St. Petersburg, Russia

2. Almazov National Medical Research Center Russia, 197341 St. Petersburg, Russia

3. School of Medicine, Nazarbayev University, 001000 Astana, Kazakhstan

4. Institute of Fundamental Medicine and Biology, Kazan Federal University, 420008 Kazan, Russia

Abstract

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.

Funder

Recruitment of the Leading Scientists into the Russian Institutions of Higher Education

Publisher

MDPI AG

Subject

Molecular Biology,Biochemistry,Endocrinology, Diabetes and Metabolism

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