Mitochondria-Mediated Apoptosis of HCC Cells Triggered by Knockdown of Glutamate Dehydrogenase 1: Perspective for Its Inhibition through Quercetin and Permethylated Anigopreissin A
| Autor: | Vittoria Infantino, Ilaria Pappalardo, Paolo Convertini, Alessandra Sardone, Maria Antonietta Di Noia, Simona Todisco, Michela Marsico, Anna Santarsiero, Lucia Chiummiento |
|---|---|
| Rok vydání: | 2021 |
| Předmět: |
Bioenergetics
QH301-705.5 Permethylated Anigopreissin A (PAA) Medicine (miscellaneous) hGDH1 General Biochemistry Genetics and Molecular Biology Article quercetin medicine Gene silencing Biology (General) HCC Gene knockdown redox homeostasis biology Chemistry apoptosis Cancer medicine.disease GLUD1 inhibition Citric acid cycle Glutamate dehydrogenase 1 Apoptosis Cancer cell Cancer research biology.protein mitochondrial mass |
| Zdroj: | Biomedicines Biomedicines, Vol 9, Iss 1664, p 1664 (2021) Volume 9 Issue 11 |
| ISSN: | 2227-9059 |
| Popis: | Metabolic reprogramming is a hallmark of cancer cells required to ensure high energy needs and the maintenance of redox balance. A relevant metabolic change of cancer cell bioenergetics is the increase in glutamine metabolism. Hepatocellular carcinoma (HCC), one of the most lethal cancer and which requires the continuous development of new therapeutic strategies, shows an up-regulation of human glutamate dehydrogenase 1 (hGDH1). GDH1 function may be relevant in cancer cells (or HCC) to drive the glutamine catabolism from L-glutamate towards the synthesis of α-ketoglutarate (α-KG), thus supplying key tricarboxylic acid cycle (TCA cycle) metabolites. Here, the effects of hGLUD1 gene silencing (siGLUD1) and GDH1 inhibition were evaluated. Our results demonstrate that siGLUD1 in HepG2 cells induces a significant reduction in cell proliferation (58.8% ± 10.63%), a decrease in BCL2 expression levels, mitochondrial mass (75% ± 5.89%), mitochondrial membrane potential (30% ± 7.06%), and a significant increase in mitochondrial superoxide anion (25% ± 6.55%) compared to control/untreated cells. The inhibition strategy leads us to identify two possible inhibitors of hGDH1: quercetin and Permethylated Anigopreissin A (PAA). These findings suggest that hGDH1 could be a potential candidate target to impair the metabolic reprogramming of HCC cells. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|