Blockade of Cellular Energy Metabolism through 6-Aminonicotinamide Reduces Proliferation of Non-Small Lung Cancer Cells by Inducing Endoplasmic Reticulum Stress

The pentose phosphate pathway (PPP) is the most common pathway in most cancer cells and stimulates antioxidant defense mechanisms and synthesis of biomolecule precursors. It is believed that cancer cells persistently ameliorate glucose flux into the PPP to maintain their anabolic requirements and ad...

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Autores principales:	Neha Kaushik, Nagendra Kumar Kaushik, Eun Ha Choi, June Hyun Kim
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	metabolic inhibitor lung cancer endoplasmic reticulum stress mitochondrial activity Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/7571381b2e2a4a03bfafeca55db34393
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spelling	oai:doaj.org-article:7571381b2e2a4a03bfafeca55db343932021-11-25T16:46:53ZBlockade of Cellular Energy Metabolism through 6-Aminonicotinamide Reduces Proliferation of Non-Small Lung Cancer Cells by Inducing Endoplasmic Reticulum Stress10.3390/biology101110882079-7737https://doaj.org/article/7571381b2e2a4a03bfafeca55db343932021-10-01T00:00:00Zhttps://www.mdpi.com/2079-7737/10/11/1088https://doaj.org/toc/2079-7737The pentose phosphate pathway (PPP) is the most common pathway in most cancer cells and stimulates antioxidant defense mechanisms and synthesis of biomolecule precursors. It is believed that cancer cells persistently ameliorate glucose flux into the PPP to maintain their anabolic requirements and adjust oxidative stress. TCGA analyses have indicated the upregulation of enzymes involved in PPP in lung cancer. Hence, the present study aimed to determine whether the pharmacological blockade of glucose 6-phosphate dehydrogenase (G6PD), the primary and rate-limiting enzyme involved in PPP, using 6-aminonicotinamide (6-AN), could induce antiproliferative activity in two lung cancer cell lines. Exposure to 6-AN suppressed lactate production and glucose consumption, modified the mitochondrial potential and redox balance, and thereby induced the endoplasmic reticulum (ER) stress to reduce lung cancer cell proliferation and govern cellular apoptosis. Collectively, this is the first study in which PPP blockade by 6-AN causes reactive oxygen species (ROS)-mediated apoptosis by ER stress in lung cancer cells. Further preclinical studies will be conducted to validate the biological applicability of these findings.Neha KaushikNagendra Kumar KaushikEun Ha ChoiJune Hyun KimMDPI AGarticlemetabolic inhibitorlung cancerendoplasmic reticulum stressmitochondrial activityBiology (General)QH301-705.5ENBiology, Vol 10, Iss 1088, p 1088 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	metabolic inhibitor lung cancer endoplasmic reticulum stress mitochondrial activity Biology (General) QH301-705.5
spellingShingle	metabolic inhibitor lung cancer endoplasmic reticulum stress mitochondrial activity Biology (General) QH301-705.5 Neha Kaushik Nagendra Kumar Kaushik Eun Ha Choi June Hyun Kim Blockade of Cellular Energy Metabolism through 6-Aminonicotinamide Reduces Proliferation of Non-Small Lung Cancer Cells by Inducing Endoplasmic Reticulum Stress
description	The pentose phosphate pathway (PPP) is the most common pathway in most cancer cells and stimulates antioxidant defense mechanisms and synthesis of biomolecule precursors. It is believed that cancer cells persistently ameliorate glucose flux into the PPP to maintain their anabolic requirements and adjust oxidative stress. TCGA analyses have indicated the upregulation of enzymes involved in PPP in lung cancer. Hence, the present study aimed to determine whether the pharmacological blockade of glucose 6-phosphate dehydrogenase (G6PD), the primary and rate-limiting enzyme involved in PPP, using 6-aminonicotinamide (6-AN), could induce antiproliferative activity in two lung cancer cell lines. Exposure to 6-AN suppressed lactate production and glucose consumption, modified the mitochondrial potential and redox balance, and thereby induced the endoplasmic reticulum (ER) stress to reduce lung cancer cell proliferation and govern cellular apoptosis. Collectively, this is the first study in which PPP blockade by 6-AN causes reactive oxygen species (ROS)-mediated apoptosis by ER stress in lung cancer cells. Further preclinical studies will be conducted to validate the biological applicability of these findings.
format	article
author	Neha Kaushik Nagendra Kumar Kaushik Eun Ha Choi June Hyun Kim
author_facet	Neha Kaushik Nagendra Kumar Kaushik Eun Ha Choi June Hyun Kim
author_sort	Neha Kaushik
title	Blockade of Cellular Energy Metabolism through 6-Aminonicotinamide Reduces Proliferation of Non-Small Lung Cancer Cells by Inducing Endoplasmic Reticulum Stress
title_short	Blockade of Cellular Energy Metabolism through 6-Aminonicotinamide Reduces Proliferation of Non-Small Lung Cancer Cells by Inducing Endoplasmic Reticulum Stress
title_full	Blockade of Cellular Energy Metabolism through 6-Aminonicotinamide Reduces Proliferation of Non-Small Lung Cancer Cells by Inducing Endoplasmic Reticulum Stress
title_fullStr	Blockade of Cellular Energy Metabolism through 6-Aminonicotinamide Reduces Proliferation of Non-Small Lung Cancer Cells by Inducing Endoplasmic Reticulum Stress
title_full_unstemmed	Blockade of Cellular Energy Metabolism through 6-Aminonicotinamide Reduces Proliferation of Non-Small Lung Cancer Cells by Inducing Endoplasmic Reticulum Stress
title_sort	blockade of cellular energy metabolism through 6-aminonicotinamide reduces proliferation of non-small lung cancer cells by inducing endoplasmic reticulum stress
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/7571381b2e2a4a03bfafeca55db34393
work_keys_str_mv	AT nehakaushik blockadeofcellularenergymetabolismthrough6aminonicotinamidereducesproliferationofnonsmalllungcancercellsbyinducingendoplasmicreticulumstress AT nagendrakumarkaushik blockadeofcellularenergymetabolismthrough6aminonicotinamidereducesproliferationofnonsmalllungcancercellsbyinducingendoplasmicreticulumstress AT eunhachoi blockadeofcellularenergymetabolismthrough6aminonicotinamidereducesproliferationofnonsmalllungcancercellsbyinducingendoplasmicreticulumstress AT junehyunkim blockadeofcellularenergymetabolismthrough6aminonicotinamidereducesproliferationofnonsmalllungcancercellsbyinducingendoplasmicreticulumstress
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Blockade of Cellular Energy Metabolism through 6-Aminonicotinamide Reduces Proliferation of Non-Small Lung Cancer Cells by Inducing Endoplasmic Reticulum Stress

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