Polydatin enhances oxaliplatin-induced cell death by activating NOX5-ROS-mediated DNA damage and ER stress in colon cancer cells

doi:10.3389/fphar.2024.1532695

科研成果详情

题名	Polydatin enhances oxaliplatin-induced cell death by activating NOX5-ROS-mediated DNA damage and ER stress in colon cancer cells
作者	Zhao, Qi 1,2,3,4,5; Zhang, Yan 1,2,3; Liu, Jieyu1,2; Chen, Peipei 3; Onga, Annabeth 3; Cho, Namki 4,5; Cui, Ri3; Zheng, Chenguo1,2
发表日期	2025-01-09
发表期刊	FRONTIERS IN PHARMACOLOGY 影响因子和分区
语种	英语
原始文献类型	Article
关键词	colorectal cancer polydatin oxaliplatin ROS NAPDH oxidase 5 DNA damage
其他关键词	APOPTOSIS ; NOX5
摘要	Background Polydatin (3,4 ',5-trihydroxy-3-beta-d-glucopyranoside, PD) is known for its antioxidant and anti-inflammatory properties. Oxaliplatin (OXA)-based chemotherapy is the first-line treatment for metastatic and recurrent colorectal cancer (CRC). However, the lack of selectivity for normal cells often results in side effects. Consequently, the search for anti-cancer components with high efficacy and low cytotoxicity has become a significant focus in recent years.Methods The anti-tumor effects of PD, OXA or their combination were assessed by cell viability, colony formation, and wound-healing assays. Reactive oxygen species (ROS) generation was measured by flow cytometry and DNA damage was assessed by immunofluorescence assay. The relative gene and protein expressions were analyzed by quantitative real time-PCR (qRT-PCR) and Western blot assays. Molecular docking analysis predicted the interaction between PD and potential targets.Results We found that PD exerted anti-CRC activity by promoting Nicotinamide Adenine Dinucleotide Phosphate (NADPH) oxidase 5 (NOX5)-mediated ROS production, activating the endoplasmic reticulum (ER) stress, and inducing DNA damage. Knocking down NOX5 attenuated the inhibition of proliferation and colony forming ability induced by PD in colon cancer cells and reversed the expression of C/EBP-homologous protein (CHOP) and activating transcription factor 4 (ATF4) proteins. In addition, combination of PD and OXA synergistically exerted anti-CRC activities by promoting DNA damage and activating ER stress signaling pathway.Conclusion The combination of PD and OXA could be an effective treatment strategy for certain patients with CRC.
资助项目	National Natural Science Foundation of China [81672305, 82274530]; Natural Science Foundation of Zhejiang Province [LZ22H160006]
出版者	FRONTIERS MEDIA SA
ISSN	1663-9812
EISSN	1663-9812
卷号	15
DOI	10.3389/fphar.2024.1532695
页数	16
WOS类目	Pharmacology & Pharmacy
WOS研究方向	Pharmacology & Pharmacy
WOS记录号	WOS:001402604900001
收录类别	SCIE ; PUBMED
URL	查看原文
PubMed ID	39850563
通讯作者地址	[Zheng, Chenguo]Wenzhou Med Univ, Affiliated Hosp 2, Wenzhou, Zhejiang, Peoples R China. ; [Zheng, Chenguo]Wenzhou Med Univ, Yuying Childrens Hosp, Wenzhou, Zhejiang, Peoples R China. ; [Cui, Ri]Wenzhou Med Univ, Canc & Anticanc Drug Res Ctr, Sch Pharmaceut Sci, Wenzhou, Zhejiang, Peoples R China. ; [Cho, Namki]Chonnam Natl Univ, Coll Pharm, Gwangju, South Korea. ; [Cho, Namki]Chonnam Natl Univ, Res Inst Drug Dev, Gwangju, South Korea.
引用统计
文献类型	期刊论文
条目标识符	https://kms.wmu.edu.cn/handle/3ETUA0LF/225513
专题	附属第二医院第二临床医学院，附属第二医院、育英儿童医院
通讯作者	Cho, Namki; Cui, Ri; Zheng, Chenguo
作者单位	1.Wenzhou Med Univ, Affiliated Hosp 2, Wenzhou, Zhejiang, Peoples R China; 2.Wenzhou Med Univ, Yuying Childrens Hosp, Wenzhou, Zhejiang, Peoples R China; 3.Wenzhou Med Univ, Canc & Anticanc Drug Res Ctr, Sch Pharmaceut Sci, Wenzhou, Zhejiang, Peoples R China; 4.Chonnam Natl Univ, Coll Pharm, Gwangju, South Korea; 5.Chonnam Natl Univ, Res Inst Drug Dev, Gwangju, South Korea
第一作者单位	附属第二医院; 第二临床医学院，附属第二医院、育英儿童医院; 温州医科大学
通讯作者单位	附属第二医院; 第二临床医学院，附属第二医院、育英儿童医院; 温州医科大学
第一作者的第一单位	附属第二医院
推荐引用方式 GB/T 7714	Zhao, Qi,Zhang, Yan,Liu, Jieyu,et al. Polydatin enhances oxaliplatin-induced cell death by activating NOX5-ROS-mediated DNA damage and ER stress in colon cancer cells[J]. FRONTIERS IN PHARMACOLOGY,2025,15.
APA	Zhao, Qi., Zhang, Yan., Liu, Jieyu., Chen, Peipei., Onga, Annabeth., ... & Zheng, Chenguo. (2025). Polydatin enhances oxaliplatin-induced cell death by activating NOX5-ROS-mediated DNA damage and ER stress in colon cancer cells. FRONTIERS IN PHARMACOLOGY, 15.
MLA	Zhao, Qi,et al."Polydatin enhances oxaliplatin-induced cell death by activating NOX5-ROS-mediated DNA damage and ER stress in colon cancer cells".FRONTIERS IN PHARMACOLOGY 15(2025).