title: S-nitrosocaptopril interrupts adhesion of cancer cells to vascular endothelium by suppressing cell adhesion molecules via inhibition of the NF-кB and JAK/STAT signal pathways in endothelial cells.
abstract: Inflammatory cytokines can induce the expression of cell adhesion molecules (CAMs) in endothelial cells. The induction may play an important role in attracting circulating tumor cells (CTCs) to endothelial cells. S-nitrosocaptopril (CapNO) is known to produce vasorelaxation and interfere the hetero-adhesion of CTCs to vascular endothelium via down-regulating the expression of CAMs. To elucidate the mechanisms underlying the inhibition of CapNO on CAMs, in this study, we examined the relationship between cytokines and CAMs expression and investigated the effects of CapNO on cytokine-induced NF-кB and JAK/STAT signal pathways. The activation of CAMs by cytokines was dependent on concentrations and reaction time of cytokines, and the combination of cytokines could produce a strong synergistic effect. IL-1β induced the expression of CAMs on endothelial cells by activating NF-кB and JAK/STAT pathways. CapNO inhibited IL-1β-stimulated NF-кB pathway by down-regulating IKK-α and inducing IкB-α directly. CapNO also inhibited JAK/STAT pathway by inhibiting JAK2 and STAT3 expressions. These effects bring about down-regulating CAMs expression on endothelial cells. These results suggest that CapNO may interrupt adhesion of cancer cells to endothelium by suppressing CAMs via inhibiting the NF-кB and JAK/STAT pathways in endothelial cells.
authors: Cancer Metastasis Alert and Prevention Center, and Biopharmaceutical Photocatalysis of State Key Laboratory of Photocatalysis on Energy and Environment, College of Chemistry, Fuzhou University, Fuzhou 350002, China.
authors: Shu
authors: S
authors: Lian
authors: Cancer Metastasis Alert and Prevention Center, and Biopharmaceutical Photocatalysis of State Key Laboratory of Photocatalysis on Energy and Environment, College of Chemistry, Fuzhou University, Fuzhou 350002, China.
authors: Yusheng
authors: Y
authors: Lu
authors: Cancer Metastasis Alert and Prevention Center, and Biopharmaceutical Photocatalysis of State Key Laboratory of Photocatalysis on Energy and Environment, College of Chemistry, Fuzhou University, Fuzhou 350002, China.
authors: Yunlong
authors: Y
authors: Cheng
authors: Cancer Metastasis Alert and Prevention Center, and Biopharmaceutical Photocatalysis of State Key Laboratory of Photocatalysis on Energy and Environment, College of Chemistry, Fuzhou University, Fuzhou 350002, China.
authors: Ting
authors: T
authors: Yu
authors: Cancer Metastasis Alert and Prevention Center, and Biopharmaceutical Photocatalysis of State Key Laboratory of Photocatalysis on Energy and Environment, College of Chemistry, Fuzhou University, Fuzhou 350002, China.
authors: Xiaodong
authors: X
authors: Xie
authors: Cancer Metastasis Alert and Prevention Center, and Biopharmaceutical Photocatalysis of State Key Laboratory of Photocatalysis on Energy and Environment, College of Chemistry, Fuzhou University, Fuzhou 350002, China.
authors: Haiyang
authors: H
authors: Liang
authors: Fujian Provincial People's Hospital Affiliated to Fujian University of Traditional Chinese Medicine, Fuzhou 350004, China.
authors: Yuying
authors: Y
authors: Ye
authors: Cancer Metastasis Alert and Prevention Center, and Biopharmaceutical Photocatalysis of State Key Laboratory of Photocatalysis on Energy and Environment, College of Chemistry, Fuzhou University, Fuzhou 350002, China. Electronic address: cmapcjia1234@163.com.
authors: Lee
authors: L
authors: Jia
mesh_terms: D000818:Animals; D002216:Captopril / Q000031:analogs & derivatives* / Q000494:pharmacology; D002448:Cell Adhesion / Q000187:drug effects; D015815:Cell Adhesion Molecules / Q000378:metabolism*; D016207:Cytokines / Q000494:pharmacology; D004357:Drug Synergism; D004730:Endothelium, Vascular / Q000187:drug effects / Q000473:pathology*; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D019073:HT29 Cells; D061307:Human Umbilical Vein Endothelial Cells / Q000166:cytology* / Q000187:drug effects; D006801:Humans; D053612:Janus Kinases / Q000378:metabolism*; D016328:NF-kappa B / Q000378:metabolism*; D009362:Neoplasm Metastasis; D050791:STAT Transcription Factors / Q000378:metabolism*; D012449:Safety; D015398:Signal Transduction / Q000187:drug effects; D013997:Time Factors
chemical_list: D015815:Cell Adhesion Molecules; D016207:Cytokines; D016328:NF-kappa B; D050791:STAT Transcription Factors; C060039:S-nitrosocaptopril; D002216:Captopril; D053612:Janus Kinases
keywords: Cancer metastatic prevention; Cell adhesion molecules; Inflammation; JAK/STAT; NF-κB; S-nitrosocaptopril