Cargando…
α-Lipoic Acid Targeting PDK1/NRF2 Axis Contributes to the Apoptosis Effect of Lung Cancer Cells
As an antioxidant, α-lipoic acid (LA) has attracted much attention to cancer research. However, the exact mechanism of LA in cancer progression control and prevention remains to be unclear. In this study, we demonstrated that α-lipoic acid has inhibitory effects on the proliferation, migration, and...
Autores principales: | , , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Hindawi
2021
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8211503/ https://www.ncbi.nlm.nih.gov/pubmed/34211631 http://dx.doi.org/10.1155/2021/6633419 |
_version_ | 1783709479477444608 |
---|---|
author | Yue, Liduo Ren, Yanbei Yue, Qingxi Ding, Zhou Wang, Kai Zheng, Tiansheng Chen, Guojie Chen, Xiangyun Li, Ming Fan, Lihong |
author_facet | Yue, Liduo Ren, Yanbei Yue, Qingxi Ding, Zhou Wang, Kai Zheng, Tiansheng Chen, Guojie Chen, Xiangyun Li, Ming Fan, Lihong |
author_sort | Yue, Liduo |
collection | PubMed |
description | As an antioxidant, α-lipoic acid (LA) has attracted much attention to cancer research. However, the exact mechanism of LA in cancer progression control and prevention remains to be unclear. In this study, we demonstrated that α-lipoic acid has inhibitory effects on the proliferation, migration, and proapoptotic effects of non-small-cell lung cancer (NSCLC) cell lines A549 and PC9. LA-induced NSCLC cell apoptosis was mediated by elevated mitochondrial reactive oxygen species (ROS). Further study confirmed that it is by downregulating the expression of PDK1 (the PDH kinase), resulted in less phospho-PDH phenotype which could interact with Keap1, the negative controller of NRF2, directly leading to NRF2 decrease. Thus, by downregulating the NRF2 antioxidant system, LA plays a role in promoting apoptosis through the ROS signaling pathway. Moreover, LA could enhance other PDK inhibitors with the proapoptosis effect. In summary, our study shows that LA promotes apoptosis and exerts its antitumor activity against lung cancer by regulating mitochondrial energy metabolism enzyme-related antioxidative stress system. Administration of LA to the tumor-bearing animal model further supported the antitumor effect of LA. These findings provided new ideas for the clinical application of LA in the field of cancer therapy. |
format | Online Article Text |
id | pubmed-8211503 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Hindawi |
record_format | MEDLINE/PubMed |
spelling | pubmed-82115032021-06-30 α-Lipoic Acid Targeting PDK1/NRF2 Axis Contributes to the Apoptosis Effect of Lung Cancer Cells Yue, Liduo Ren, Yanbei Yue, Qingxi Ding, Zhou Wang, Kai Zheng, Tiansheng Chen, Guojie Chen, Xiangyun Li, Ming Fan, Lihong Oxid Med Cell Longev Research Article As an antioxidant, α-lipoic acid (LA) has attracted much attention to cancer research. However, the exact mechanism of LA in cancer progression control and prevention remains to be unclear. In this study, we demonstrated that α-lipoic acid has inhibitory effects on the proliferation, migration, and proapoptotic effects of non-small-cell lung cancer (NSCLC) cell lines A549 and PC9. LA-induced NSCLC cell apoptosis was mediated by elevated mitochondrial reactive oxygen species (ROS). Further study confirmed that it is by downregulating the expression of PDK1 (the PDH kinase), resulted in less phospho-PDH phenotype which could interact with Keap1, the negative controller of NRF2, directly leading to NRF2 decrease. Thus, by downregulating the NRF2 antioxidant system, LA plays a role in promoting apoptosis through the ROS signaling pathway. Moreover, LA could enhance other PDK inhibitors with the proapoptosis effect. In summary, our study shows that LA promotes apoptosis and exerts its antitumor activity against lung cancer by regulating mitochondrial energy metabolism enzyme-related antioxidative stress system. Administration of LA to the tumor-bearing animal model further supported the antitumor effect of LA. These findings provided new ideas for the clinical application of LA in the field of cancer therapy. Hindawi 2021-06-04 /pmc/articles/PMC8211503/ /pubmed/34211631 http://dx.doi.org/10.1155/2021/6633419 Text en Copyright © 2021 Liduo Yue et al. https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Research Article Yue, Liduo Ren, Yanbei Yue, Qingxi Ding, Zhou Wang, Kai Zheng, Tiansheng Chen, Guojie Chen, Xiangyun Li, Ming Fan, Lihong α-Lipoic Acid Targeting PDK1/NRF2 Axis Contributes to the Apoptosis Effect of Lung Cancer Cells |
title |
α-Lipoic Acid Targeting PDK1/NRF2 Axis Contributes to the Apoptosis Effect of Lung Cancer Cells |
title_full |
α-Lipoic Acid Targeting PDK1/NRF2 Axis Contributes to the Apoptosis Effect of Lung Cancer Cells |
title_fullStr |
α-Lipoic Acid Targeting PDK1/NRF2 Axis Contributes to the Apoptosis Effect of Lung Cancer Cells |
title_full_unstemmed |
α-Lipoic Acid Targeting PDK1/NRF2 Axis Contributes to the Apoptosis Effect of Lung Cancer Cells |
title_short |
α-Lipoic Acid Targeting PDK1/NRF2 Axis Contributes to the Apoptosis Effect of Lung Cancer Cells |
title_sort | α-lipoic acid targeting pdk1/nrf2 axis contributes to the apoptosis effect of lung cancer cells |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8211503/ https://www.ncbi.nlm.nih.gov/pubmed/34211631 http://dx.doi.org/10.1155/2021/6633419 |
work_keys_str_mv | AT yueliduo alipoicacidtargetingpdk1nrf2axiscontributestotheapoptosiseffectoflungcancercells AT renyanbei alipoicacidtargetingpdk1nrf2axiscontributestotheapoptosiseffectoflungcancercells AT yueqingxi alipoicacidtargetingpdk1nrf2axiscontributestotheapoptosiseffectoflungcancercells AT dingzhou alipoicacidtargetingpdk1nrf2axiscontributestotheapoptosiseffectoflungcancercells AT wangkai alipoicacidtargetingpdk1nrf2axiscontributestotheapoptosiseffectoflungcancercells AT zhengtiansheng alipoicacidtargetingpdk1nrf2axiscontributestotheapoptosiseffectoflungcancercells AT chenguojie alipoicacidtargetingpdk1nrf2axiscontributestotheapoptosiseffectoflungcancercells AT chenxiangyun alipoicacidtargetingpdk1nrf2axiscontributestotheapoptosiseffectoflungcancercells AT liming alipoicacidtargetingpdk1nrf2axiscontributestotheapoptosiseffectoflungcancercells AT fanlihong alipoicacidtargetingpdk1nrf2axiscontributestotheapoptosiseffectoflungcancercells |