Shuvalov Oleg, Kirdeeva Yulia, Fefilova Elizaveta, Netsvetay Sofia, Zorin Mark, Vlasova Yulia, Fedorova Olga, Daks Alexandra, Parfenyev Sergey, Barlev Nickolai
Institute of Cytology, Russian Academy of Sciences, 194064 St. Petersburg, Russia.
Almazov National Medical Research Center Russia, 197341 St. Petersburg, Russia.
Metabolites. 2023 May 15;13(5):656. doi: 10.3390/metabo13050656.
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-羟基蜕皮酮（20E）是一种节肢动物激素，一些植物将其作为防御机制的一部分进行合成。在人类中，20E没有激素活性，但具有许多有益的药理特性，包括合成代谢、适应原性、降血糖和抗氧化特性，以及心脏、肝脏和神经保护作用。最近的研究表明，20E也可能具有抗肿瘤活性。在本研究中，我们揭示了20E在非小细胞肺癌（NSCLC）细胞系中的抗癌特性。20E表现出显著的抗氧化能力，并诱导抗氧化应激反应基因的表达。对20E处理的肺癌细胞进行RNA测序分析发现，参与不同代谢过程的基因表达减弱。事实上，20E分别抑制了糖酵解和一碳代谢的几种酶及其关键转录调节因子——c-Myc和ATF4。因此，使用海马能量分析方法，我们观察到20E处理介导的糖酵解和呼吸作用受到抑制。此外，20E使肺癌细胞对代谢抑制剂敏感，并显著抑制癌症干细胞（CSCs）标志物的表达。因此，除了20E已知的有益药理活性外，我们的数据还揭示了20E在NSCLC细胞中的新型抗肿瘤特性。
