Mitochondria-Mediated Apoptosis of HCC Cells Triggered by Knockdown of Glutamate Dehydrogenase 1: Perspective for Its Inhibition through Quercetin and Permethylated Anigopreissin A

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 r...

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Autores principales:	Michela Marsico, Anna Santarsiero, Ilaria Pappalardo, Paolo Convertini, Lucia Chiummiento, Alessandra Sardone, Maria Antonietta Di Noia, Vittoria Infantino, Simona Todisco
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	hGDH1 HCC <i>GLUD1</i> redox homeostasis mitochondrial mass apoptosis Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/d8d0a8dc69f7402cb4ae165d50db02a1
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spelling	oai:doaj.org-article:d8d0a8dc69f7402cb4ae165d50db02a12021-11-25T16:50:28ZMitochondria-Mediated Apoptosis of HCC Cells Triggered by Knockdown of Glutamate Dehydrogenase 1: Perspective for Its Inhibition through Quercetin and Permethylated Anigopreissin A10.3390/biomedicines91116642227-9059https://doaj.org/article/d8d0a8dc69f7402cb4ae165d50db02a12021-11-01T00:00:00Zhttps://www.mdpi.com/2227-9059/9/11/1664https://doaj.org/toc/2227-9059Metabolic 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 h<i>GLUD1</i> gene silencing (si<i>GLUD1</i>) and GDH1 inhibition were evaluated. Our results demonstrate that si<i>GLUD1</i> 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.Michela MarsicoAnna SantarsieroIlaria PappalardoPaolo ConvertiniLucia ChiummientoAlessandra SardoneMaria Antonietta Di NoiaVittoria InfantinoSimona TodiscoMDPI AGarticlehGDH1HCC<i>GLUD1</i>redox homeostasismitochondrial massapoptosisBiology (General)QH301-705.5ENBiomedicines, Vol 9, Iss 1664, p 1664 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	hGDH1 HCC <i>GLUD1</i> redox homeostasis mitochondrial mass apoptosis Biology (General) QH301-705.5
spellingShingle	hGDH1 HCC <i>GLUD1</i> redox homeostasis mitochondrial mass apoptosis Biology (General) QH301-705.5 Michela Marsico Anna Santarsiero Ilaria Pappalardo Paolo Convertini Lucia Chiummiento Alessandra Sardone Maria Antonietta Di Noia Vittoria Infantino Simona Todisco Mitochondria-Mediated Apoptosis of HCC Cells Triggered by Knockdown of Glutamate Dehydrogenase 1: Perspective for Its Inhibition through Quercetin and Permethylated Anigopreissin A
description	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 h<i>GLUD1</i> gene silencing (si<i>GLUD1</i>) and GDH1 inhibition were evaluated. Our results demonstrate that si<i>GLUD1</i> 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.
format	article
author	Michela Marsico Anna Santarsiero Ilaria Pappalardo Paolo Convertini Lucia Chiummiento Alessandra Sardone Maria Antonietta Di Noia Vittoria Infantino Simona Todisco
author_facet	Michela Marsico Anna Santarsiero Ilaria Pappalardo Paolo Convertini Lucia Chiummiento Alessandra Sardone Maria Antonietta Di Noia Vittoria Infantino Simona Todisco
author_sort	Michela Marsico
title	Mitochondria-Mediated Apoptosis of HCC Cells Triggered by Knockdown of Glutamate Dehydrogenase 1: Perspective for Its Inhibition through Quercetin and Permethylated Anigopreissin A
title_short	Mitochondria-Mediated Apoptosis of HCC Cells Triggered by Knockdown of Glutamate Dehydrogenase 1: Perspective for Its Inhibition through Quercetin and Permethylated Anigopreissin A
title_full	Mitochondria-Mediated Apoptosis of HCC Cells Triggered by Knockdown of Glutamate Dehydrogenase 1: Perspective for Its Inhibition through Quercetin and Permethylated Anigopreissin A
title_fullStr	Mitochondria-Mediated Apoptosis of HCC Cells Triggered by Knockdown of Glutamate Dehydrogenase 1: Perspective for Its Inhibition through Quercetin and Permethylated Anigopreissin A
title_full_unstemmed	Mitochondria-Mediated Apoptosis of HCC Cells Triggered by Knockdown of Glutamate Dehydrogenase 1: Perspective for Its Inhibition through Quercetin and Permethylated Anigopreissin A
title_sort	mitochondria-mediated apoptosis of hcc cells triggered by knockdown of glutamate dehydrogenase 1: perspective for its inhibition through quercetin and permethylated anigopreissin a
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/d8d0a8dc69f7402cb4ae165d50db02a1
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Mitochondria-Mediated Apoptosis of HCC Cells Triggered by Knockdown of Glutamate Dehydrogenase 1: Perspective for Its Inhibition through Quercetin and Permethylated Anigopreissin A

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