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

Autor:	Deng H; 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., Liu Q; Department of Pharmacology, Hainan Medical University, Haikou, Hainan 571199, China., Yu S; Department of Pathology, Guangzhou Panyu Central Hospital, Guangzhou, Guangdong 511400, China., Zhong L; Research Center for Drug Safety Evaluation of Hainan Province, Haikou, Hainan 571199, China.; Hainan Province Key Laboratory for Drug Preclinical Study of Pharmacology and Toxicology Research, Hainan Medical University, Haikou, Hainan 571199, China., Gan L; Research Center for Drug Safety Evaluation of Hainan Province, Haikou, Hainan 571199, China.; Hainan Province Key Laboratory for Drug Preclinical Study of Pharmacology and Toxicology Research, Hainan Medical University, Haikou, Hainan 571199, China., Gu H; Department of Pharmacology, Hainan Medical University, Haikou, Hainan 571199, China., Wang Q; Research Center for Drug Safety Evaluation of Hainan Province, Haikou, Hainan 571199, China.; Hainan Province Key Laboratory for Drug Preclinical Study of Pharmacology and Toxicology Research, Hainan Medical University, Haikou, Hainan 571199, China., Cheng R; Research Center for Drug Safety Evaluation of Hainan Province, Haikou, Hainan 571199, China.; Hainan Province Key Laboratory for Drug Preclinical Study of Pharmacology and Toxicology Research, Hainan Medical University, Haikou, Hainan 571199, China., Liu Y; Department of Gastrointestinal Surgery, Huazhong University of Science and Technology Union Shenzhen Hospital, Shenzhen, Guangdong 518000, China., Liu L; Department of Gastrointestinal Surgery, Huazhong University of Science and Technology Union Shenzhen Hospital, Shenzhen, Guangdong 518000, China., Huang L; Research Center for Drug Safety Evaluation of Hainan Province, Haikou, Hainan 571199, 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., Xu R; Department of Gastrointestinal Surgery, Huazhong University of Science and Technology Union Shenzhen Hospital, Shenzhen, Guangdong 518000, China.
Jazyk:	angličtina
Zdroj:	Genes & diseases [Genes Dis] 2023 Apr 13; Vol. 11 (5), pp. 100938. Date of Electronic Publication: 2023 Apr 13 (Print Publication: 2024).
DOI:	10.1016/j.gendis.2023.03.014
Abstrakt:	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-inflammatory and antitumor actions. The effects of narciclasine on colorectal tumors were evaluated, 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 murine xenografts. The results of flow cytometry on JC-1 and Annexin V/PI revealed that narciclasine significantly reduced the mitochondrial 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, Caspase-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 narciclasine 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-κB anti-apoptotic signaling pathway. (© 2023 The Authors. Publishing services by Elsevier B.V. on behalf of KeAi Communications Co., Ltd.)
Databáze:	MEDLINE
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