Quercetin inhibits DNA damage responses to induce apoptosis via SIRT5/PI3K/AKT pathway in non-small cell lung cancer
SIRT5 is a mitochondrial NAD+ -dependent lysine deacylase. Downregulation of SIRT5 has been linked to several primary cancers and DNA damage. In clinical therapy for non-small cell lung cancer (NSCLC), the Feiyiliu Mixture (FYLM) is an experience and effective Chinese herb prescription. And we found...
Main Authors: | , , , , , |
---|---|
Format: | Article |
Language: | English |
Published: |
Elsevier
2023-09-01
|
Series: | Biomedicine & Pharmacotherapy |
Subjects: | |
Online Access: | http://www.sciencedirect.com/science/article/pii/S0753332223008624 |
_version_ | 1797744154624655360 |
---|---|
author | Baochen Zhou Ye Yang Xuemeng Pang Jingjing Shi Ting Jiang Xin Zheng |
author_facet | Baochen Zhou Ye Yang Xuemeng Pang Jingjing Shi Ting Jiang Xin Zheng |
author_sort | Baochen Zhou |
collection | DOAJ |
description | SIRT5 is a mitochondrial NAD+ -dependent lysine deacylase. Downregulation of SIRT5 has been linked to several primary cancers and DNA damage. In clinical therapy for non-small cell lung cancer (NSCLC), the Feiyiliu Mixture (FYLM) is an experience and effective Chinese herb prescription. And we found that quercetin is an important ingredient in the FYLM. However, whether quercetin regulates DNA damage repair (DDR) and induces apoptosis through SIRT5 in NSCLC remains unknown. The present study revealed that quercetin directly binds to SIRT5 and inhibits the phosphorylation of PI3K/AKT through the interaction between SIRT5 and PI3K, thus inhibiting the repair process of homologous recombination (HR) and non-homologous end-joining (NHEJ) in NSCLC, which raise mitotic catastrophe and apoptosis. Our study provided a novel mechanism of action of quercetin in the treatment of NSCLC. |
first_indexed | 2024-03-12T15:05:40Z |
format | Article |
id | doaj.art-c3d9281b66a347f9a5b6b40d797e2aad |
institution | Directory Open Access Journal |
issn | 0753-3322 |
language | English |
last_indexed | 2024-03-12T15:05:40Z |
publishDate | 2023-09-01 |
publisher | Elsevier |
record_format | Article |
series | Biomedicine & Pharmacotherapy |
spelling | doaj.art-c3d9281b66a347f9a5b6b40d797e2aad2023-08-13T04:52:29ZengElsevierBiomedicine & Pharmacotherapy0753-33222023-09-01165115071Quercetin inhibits DNA damage responses to induce apoptosis via SIRT5/PI3K/AKT pathway in non-small cell lung cancerBaochen Zhou0Ye Yang1Xuemeng Pang2Jingjing Shi3Ting Jiang4Xin Zheng5Shandong University of Traditional Chinese Medicine, Jinan 250355, China; Qingdao Hiser Hospital Affiliated of Qingdao University (Qingdao Traditional Chinese Medicine Hospital), Qingdao 266033, ChinaQingdao Central Hospital, Qingdao 266042, ChinaShandong University of Traditional Chinese Medicine, Jinan 250355, ChinaShandong University of Traditional Chinese Medicine, Jinan 250355, ChinaQingdao Hiser Hospital Affiliated of Qingdao University (Qingdao Traditional Chinese Medicine Hospital), Qingdao 266033, ChinaShandong University of Traditional Chinese Medicine, Jinan 250355, China; Qingdao Hiser Hospital Affiliated of Qingdao University (Qingdao Traditional Chinese Medicine Hospital), Qingdao 266033, China; Corresponding author at: Qingdao Hiser Hospital Affiliated of Qingdao University (Qingdao Traditional Chinese Medicine Hospital), Qingdao 266033, China.SIRT5 is a mitochondrial NAD+ -dependent lysine deacylase. Downregulation of SIRT5 has been linked to several primary cancers and DNA damage. In clinical therapy for non-small cell lung cancer (NSCLC), the Feiyiliu Mixture (FYLM) is an experience and effective Chinese herb prescription. And we found that quercetin is an important ingredient in the FYLM. However, whether quercetin regulates DNA damage repair (DDR) and induces apoptosis through SIRT5 in NSCLC remains unknown. The present study revealed that quercetin directly binds to SIRT5 and inhibits the phosphorylation of PI3K/AKT through the interaction between SIRT5 and PI3K, thus inhibiting the repair process of homologous recombination (HR) and non-homologous end-joining (NHEJ) in NSCLC, which raise mitotic catastrophe and apoptosis. Our study provided a novel mechanism of action of quercetin in the treatment of NSCLC.http://www.sciencedirect.com/science/article/pii/S0753332223008624QuercetinSIRT5PI3K/AKTNSCLCDDRMitotic catastrophe |
spellingShingle | Baochen Zhou Ye Yang Xuemeng Pang Jingjing Shi Ting Jiang Xin Zheng Quercetin inhibits DNA damage responses to induce apoptosis via SIRT5/PI3K/AKT pathway in non-small cell lung cancer Biomedicine & Pharmacotherapy Quercetin SIRT5 PI3K/AKT NSCLC DDR Mitotic catastrophe |
title | Quercetin inhibits DNA damage responses to induce apoptosis via SIRT5/PI3K/AKT pathway in non-small cell lung cancer |
title_full | Quercetin inhibits DNA damage responses to induce apoptosis via SIRT5/PI3K/AKT pathway in non-small cell lung cancer |
title_fullStr | Quercetin inhibits DNA damage responses to induce apoptosis via SIRT5/PI3K/AKT pathway in non-small cell lung cancer |
title_full_unstemmed | Quercetin inhibits DNA damage responses to induce apoptosis via SIRT5/PI3K/AKT pathway in non-small cell lung cancer |
title_short | Quercetin inhibits DNA damage responses to induce apoptosis via SIRT5/PI3K/AKT pathway in non-small cell lung cancer |
title_sort | quercetin inhibits dna damage responses to induce apoptosis via sirt5 pi3k akt pathway in non small cell lung cancer |
topic | Quercetin SIRT5 PI3K/AKT NSCLC DDR Mitotic catastrophe |
url | http://www.sciencedirect.com/science/article/pii/S0753332223008624 |
work_keys_str_mv | AT baochenzhou quercetininhibitsdnadamageresponsestoinduceapoptosisviasirt5pi3kaktpathwayinnonsmallcelllungcancer AT yeyang quercetininhibitsdnadamageresponsestoinduceapoptosisviasirt5pi3kaktpathwayinnonsmallcelllungcancer AT xuemengpang quercetininhibitsdnadamageresponsestoinduceapoptosisviasirt5pi3kaktpathwayinnonsmallcelllungcancer AT jingjingshi quercetininhibitsdnadamageresponsestoinduceapoptosisviasirt5pi3kaktpathwayinnonsmallcelllungcancer AT tingjiang quercetininhibitsdnadamageresponsestoinduceapoptosisviasirt5pi3kaktpathwayinnonsmallcelllungcancer AT xinzheng quercetininhibitsdnadamageresponsestoinduceapoptosisviasirt5pi3kaktpathwayinnonsmallcelllungcancer |