Narciclasine induces colon carcinoma cell apoptosis by inhibiting the IL-17A/Act1/TRAF6/NF-κB signaling pathway

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外文摘要：IL-17 A is a promoter of colorectal cancer initiation and progression.Narciclasine is a polyhydroxy alkaloid compound isolated from Narcissus plants,which has potent anti-inflam-matory and antitumor actions.The effects of narciclasine on colorectal tumors were evalu-ated,with a focus on IL-17 A.Narciclasine reduced the growth of HCT-116 and SW-480 colon cancer cells in vitro and in vivo in munne xenografts.The results of flow cytometry on JC-1 and Annexin V/PI revealed that narciclasine significantly reduced the mitochondnal membrane potential and induced apoptosis,findings confirmed by western blotting results of reduced Bcl-2 and enhanced Bax expression,as well as accumulation of cleaved Caspase-3,Caspase-8,Cas-pase-9,and cytoplasmic Cytochrome-c.After narciclasine incubation,IL-17 A,Act1,and TRAF6 were down-regulated,while p-P65(Ser536)accumulated in the cytoplasm,a finding confirmed by laser scanning confocal microscopy.IL17A substitution could partly reverse these narcicla-sine effects while they were elevated by IL17A silencing.Moreover,IL-17 A,Act1,and TRAF6 were significantly expressed to greater extents in human colorectal cancer compared to normal adjacent tissue specimens and were closely linked with a poor prognosis.This study provided evidence that narciclasine may be a useful therapeutic drug for colorectal cancer treatment through its actions in down-regulating the L-17A/Act1/TRAF6/NF-KB anti-apoptotic signaling pathway.

外文关键词：

Act1ApoptosisColonrectal cancerIL-17ANarciclasineNF-κB

作者：

Huiming Deng、Qiang Liu、Siman Yu、Lifan Zhong、Lianfang Gan、Huiquan Gu、Qianru Wang、Ruxin Cheng、Yong Liu、Li Liu、Ling Huang、Ronghua Xu

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作者单位：

Department of Gastrointestinal Surgery,Huazhong University of Science and Technology Union Shenzhen Hospital,Shenzhen,Guangdong 518000,China

Research Center for Drug Safety Evaluation of Hainan Province,Haikou,Hainan 571199,China

Department of Pharmacology,Hainan Medical University,Haikou,Hainan 571199,China

Department of Pathology,Guangzhou Panyu Central Hospital,Guangzhou,Guangdong 511400,China

Hainan Province Key Laboratory for Drug Preclinical Study of Pharmacology and Toxicology Research,Hainan Medical University,Haikou,Hainan 571199,China

Hainan Center for Drug and Medical Device Evaluation and Service,Hainan Medical Products Administration,Haikou,Hainan 570216,China

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基金：

Shenzhen science and Technology PlanNational Natural Science Foundation of ChinaNational Natural Science Foundation of ChinaNational Natural Science Foundation of ChinaNanshan District of Shenzhen Science and Technology Project(China)

项目编号：

JCYJ202205301420090218206067882060851817606742019057

出版年：

2024

DOI：

10.1016/j.gendis.2023.03.014

基因与疾病(英文)

ISSN：

年,卷(期)：2024.11(5)