20-Hydroxyecdysone confers antioxidant and antineoplastic properties in human non-small cell lung cancer cells

20-Hydroxyecdysone (20E) is a hormone of arthropods which is synthesized by some plants as a defense. In human, 20E has no hormonal activity but possesses a number of beneficial pharmacological properties including anabolic, adaptogenic, hypoglycemic, antioxidant, cardio-, hepato- and neuroprotective, etc. It has been used by sportsmen and is involved in clinical studies to treat several diseases. Recent studies have shown that 20E may also possess the antineoplastic activity. In the present study, we have revealed anticancer properties of 20E in Non-Small Cell Lung Cancer (NSCLC) cell lines. 20E displayed significant antioxidant capacities and induced the expression of antioxidant response genes. RNA-seq analysis of 20E-treated lung cancer cells has revealed the down-regulation of genes which are involved in different metabolic processes. Indeed, 20E suppressed enzymes of glycolysis and one-carbon metabolism, as well as their key transcriptional regulators -- c-Myc and ATF4. Using SeaHorse energy profiling approach, we have observed 20E-mediated inhibition of glycolysis and respiration. Furthermore, 20E sensibilized lung cancer cells to metabolic inhibitors and markedly suppressed the expression of CSCs markers. In addition to known beneficial pharmacological activities of 20E, our data uncover its antineoplastic properties in NSCLC cells.