NL13, a novel curcumin analogue and polo like kinase 4 inhibitor, induces cell cycle arrest and apoptosis in prostate cancer models

doi:10.1111/bph.16501

科研成果详情

题名	NL13, a novel curcumin analogue and polo like kinase 4 inhibitor, induces cell cycle arrest and apoptosis in prostate cancer models
作者	Qiao, Xinyi1,2,3,4,5,6; Zheng, Ke1,2,3,4,5,6; Ye, Lei1,2,3,4,5,6; Yang, Jin 1,2,3,4,5,6; Cui, Rong1,2,3,4,5,6; Shan, Yuanyuan 2,6; Li, Xiaoheng 1,2,3,4,5; Li, Huitao1,2,3,4,5; Zhu, Qiqi1,2,3,4,5; Zhao, Zhiguang2,6; Ge, Ren-shan1,2,3,4,5,6; Wang, Yiyan 1,2,3,4,5,6
发表日期	2024-08-14
发表期刊	British Journal of Pharmacology 影响因子和分区
语种	英语
原始文献类型	Article ; Early Access
关键词	apoptosis cell cycle curcumin analogue polo like kinase 4 prostate cancer
其他关键词	CONCISE GUIDE ; PLK4 ; ANTIOXIDANT ; EXPRESSION ; STABILITY ; PATHWAY ; ROLES
摘要	Background and PurposeProstate cancer remains a major public health burden worldwide. Polo like kinase 4 (PLK4) has emerged as a promising therapeutic target in prostate cancer due to its key roles in cell cycle regulation and tumour progression. This study aims to develop and characterize the novel curcumin analogue NL13 as a potential therapeutic agent and PLK4 inhibitor against prostate cancer.Experimental ApproachNL13 was synthesized and its effects were evaluated in prostate cancer cells and mouse xenograft models. Kinome screening and molecular modelling identified PLK4 as the primary target. Antiproliferative and proapoptotic mechanisms were explored via cell cycle, apoptosis, gene and protein analyses.Key ResultsCompared with curcumin, NL13 exhibited much greater potency in inhibiting PC3 (IC50, 3.51 mu M vs. 35.45 mu M) and DU145 (IC50, 2.53 mu M vs. 29.35 mu M) prostate cancer cells viability and PLK4 kinase activity (2.32 mu M vs. 246.88 mu M). NL13 induced G2/M cell cycle arrest through CCNB1/CDK1 down-regulation and triggered apoptosis via caspase-9/caspase-3 cleavage. These effects were mediated by PLK4 inhibition, which led to the inactivation of the AKT signalling pathway. In mice, NL13 significantly inhibited tumour growth and modulated molecular markers consistent with in vitro findings, including decreased p-AKT and increased cleaved caspase-9/3.Conclusion and ImplicationsNL13, a novel PLK4-targeted curcumin analogue, exerts promising anticancer properties against prostate cancer by disrupting the PLK4-AKT-CCNB1/CDK1 and apoptosis pathways. NL13 represents a promising new agent for prostate cancer therapy.
资助项目	National Natural Science Foundation of China [81901467, 82371610]
出版者	WILEY
ISSN	0007-1188
EISSN	1476-5381
卷号	181 期号:22 页码:4658-4676
DOI	10.1111/bph.16501
页数	19
WOS类目	Pharmacology & Pharmacy
WOS研究方向	Pharmacology & Pharmacy
WOS记录号	WOS:001290574800001
收录类别	SCIE ; PUBMED ; SCOPUS
URL	查看原文
PubMed ID	39142876
SCOPUSEID	2-s2.0-85201088892
通讯作者地址	[Ge, Ren-shan;Wang, Yiyan]Wenzhou Med Univ, Affiliated Hosp 2, Dept Anesthesiol & Perioperat Med, Wenzhou 325027, Zhejiang, Peoples R China. ; [Ge, Ren-shan;Wang, Yiyan]Wenzhou Med Univ, Yuying Childrens Hosp, Wenzhou 325027, Zhejiang, Peoples R China.
Scopus学科分类	Pharmacology
SCOPUS_ID	SCOPUS_ID:85201088892
引用统计
文献类型	期刊论文
条目标识符	https://kms.wmu.edu.cn/handle/3ETUA0LF/217444
专题	附属第二医院第二临床医学院、附属第二医院、育英儿童医院附属第二医院_病理科第二临床医学院、附属第二医院、育英儿童医院_病理学附属第二医院_麻醉科附属第二医院_麻醉重点学科实验室
通讯作者	Ge, Ren-shan; Wang, Yiyan
作者单位	1.Wenzhou Med Univ, Affiliated Hosp 2, Dept Anesthesiol & Perioperat Med, Wenzhou 325027, Zhejiang, Peoples R China; 2.Wenzhou Med Univ, Yuying Childrens Hosp, Wenzhou 325027, Zhejiang, Peoples R China; 3.Wenzhou Med Univ, Key Lab Pediat Anesthesiol, Minist Educ, Wenzhou, Zhejiang, Peoples R China; 4.Wenzhou Med Univ, Key Lab Anesthesiol Zhejiang Prov, Wenzhou, Zhejiang, Peoples R China; 5.Key Lab Environm & Male Reprod Med Wenzhou, Wenzhou, Zhejiang, Peoples R China; 6.Wenzhou Med Univ, Affiliated Hosp 2, Dept Pathol, Wenzhou, Zhejiang, Peoples R China
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; 麻醉科; 温州医科大学; 麻醉重点学科实验室; 病理科; 病理学
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; 麻醉科
第一作者的第一单位	附属第二医院
推荐引用方式 GB/T 7714	Qiao, Xinyi,Zheng, Ke,Ye, Lei,et al. NL13, a novel curcumin analogue and polo like kinase 4 inhibitor, induces cell cycle arrest and apoptosis in prostate cancer models[J]. British Journal of Pharmacology,2024,181(22):4658-4676.
APA	Qiao, Xinyi., Zheng, Ke., Ye, Lei., Yang, Jin., Cui, Rong., ... & Wang, Yiyan. (2024). NL13, a novel curcumin analogue and polo like kinase 4 inhibitor, induces cell cycle arrest and apoptosis in prostate cancer models. British Journal of Pharmacology, 181(22), 4658-4676.
MLA	Qiao, Xinyi,et al."NL13, a novel curcumin analogue and polo like kinase 4 inhibitor, induces cell cycle arrest and apoptosis in prostate cancer models".British Journal of Pharmacology 181.22(2024):4658-4676.