Aspirin attenuates vinorelbine-induced endothelial inflammation via modulating SIRT1/AMPK axis

Kun-Ling Tsai, Po Hsun Huang, Chung Lan Kao, Hsin Bang Leu, Yung Hsin Cheng, Yi Wen Liao, Yi Ping Yang, Yueh Chien, Chien Ying Wang, Chen Yuan Hsiao, Shih Hwa Chiou, Jaw Wen Chen, Shing Jong Lin

Research output: Contribution to journalArticle

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Abstract

Vinorelbine (VNR), a semisynthetic vinca alkaloid acquired from vinblastine, is frequently used as the candidate for intervention of solid tumors. Nevertheless, VNR-caused endothelial injuries may lead a mitigative effect of clinical treatment efficiency. A growing body of evidence reveals that aspirin is a potent antioxidant and anti-inflammation drug. We investigated whether aspirin attenuate VNR-induced endothelial dysfunction. Human endothelial cells (EA.hy 926) were treated with VNR to cause endothelial inflammation. Western blotting, ROS assay, ELISA were used to confirm the anti-inflammatory effect of aspirin. We confirmed that VNR supresses SIRT1 expression, reduced LKB1 and AMPK phosphorylation as well as enriched PKC activation in treated endothelial cells. Furthermore, the membrane translocation assay displayed that the levels of NADPH oxidase subunits p47phox and Rac-1 in membrane fractions of endothelial cells were higher in cells that had been treated with VNR for than in untreated cells. We corroborated that treatment of Aspirin significantly diminishes VNR-repressed SIRT1, LKB1 and AMPK phosphorylation and VNR-promoted NADPH oxidase activation, however, those findings were vanished by SIRT1 and AMPK siRNAs. Our data also shown that Aspirin represses VNR-activated TGF-beta-activated kinase-1 (TAK1) activation, inhibited the interaction of TAK1/TAK-binding protein1 (TAB1), suppressed NF-kappa B activation and pro-inflammatory cytokine secretion. We demonstrated a novel connection between VNR-caused oxidative damages and endothelial dysfunction, and provide further insight into the protective effects of aspirin in VNR-caused endothelial dysfunction.

Original languageEnglish
Pages (from-to)189-200
Number of pages12
JournalBiochemical Pharmacology
Volume88
Issue number2
DOIs
Publication statusPublished - 2014 Mar 15

Fingerprint

AMP-Activated Protein Kinases
Aspirin
Inflammation
Endothelial cells
Chemical activation
Phosphorylation
Endothelial Cells
NADPH Oxidase
Assays
vinorelbine
Vinca Alkaloids
Membranes
Vinblastine
NF-kappa B
Tumors
Anti-Inflammatory Agents
Antioxidants
Western Blotting
Enzyme-Linked Immunosorbent Assay
Cytokines

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Pharmacology

Cite this

Tsai, Kun-Ling ; Huang, Po Hsun ; Kao, Chung Lan ; Leu, Hsin Bang ; Cheng, Yung Hsin ; Liao, Yi Wen ; Yang, Yi Ping ; Chien, Yueh ; Wang, Chien Ying ; Hsiao, Chen Yuan ; Chiou, Shih Hwa ; Chen, Jaw Wen ; Lin, Shing Jong. / Aspirin attenuates vinorelbine-induced endothelial inflammation via modulating SIRT1/AMPK axis. In: Biochemical Pharmacology. 2014 ; Vol. 88, No. 2. pp. 189-200.
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title = "Aspirin attenuates vinorelbine-induced endothelial inflammation via modulating SIRT1/AMPK axis",
abstract = "Vinorelbine (VNR), a semisynthetic vinca alkaloid acquired from vinblastine, is frequently used as the candidate for intervention of solid tumors. Nevertheless, VNR-caused endothelial injuries may lead a mitigative effect of clinical treatment efficiency. A growing body of evidence reveals that aspirin is a potent antioxidant and anti-inflammation drug. We investigated whether aspirin attenuate VNR-induced endothelial dysfunction. Human endothelial cells (EA.hy 926) were treated with VNR to cause endothelial inflammation. Western blotting, ROS assay, ELISA were used to confirm the anti-inflammatory effect of aspirin. We confirmed that VNR supresses SIRT1 expression, reduced LKB1 and AMPK phosphorylation as well as enriched PKC activation in treated endothelial cells. Furthermore, the membrane translocation assay displayed that the levels of NADPH oxidase subunits p47phox and Rac-1 in membrane fractions of endothelial cells were higher in cells that had been treated with VNR for than in untreated cells. We corroborated that treatment of Aspirin significantly diminishes VNR-repressed SIRT1, LKB1 and AMPK phosphorylation and VNR-promoted NADPH oxidase activation, however, those findings were vanished by SIRT1 and AMPK siRNAs. Our data also shown that Aspirin represses VNR-activated TGF-beta-activated kinase-1 (TAK1) activation, inhibited the interaction of TAK1/TAK-binding protein1 (TAB1), suppressed NF-kappa B activation and pro-inflammatory cytokine secretion. We demonstrated a novel connection between VNR-caused oxidative damages and endothelial dysfunction, and provide further insight into the protective effects of aspirin in VNR-caused endothelial dysfunction.",
author = "Kun-Ling Tsai and Huang, {Po Hsun} and Kao, {Chung Lan} and Leu, {Hsin Bang} and Cheng, {Yung Hsin} and Liao, {Yi Wen} and Yang, {Yi Ping} and Yueh Chien and Wang, {Chien Ying} and Hsiao, {Chen Yuan} and Chiou, {Shih Hwa} and Chen, {Jaw Wen} and Lin, {Shing Jong}",
year = "2014",
month = "3",
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Tsai, K-L, Huang, PH, Kao, CL, Leu, HB, Cheng, YH, Liao, YW, Yang, YP, Chien, Y, Wang, CY, Hsiao, CY, Chiou, SH, Chen, JW & Lin, SJ 2014, 'Aspirin attenuates vinorelbine-induced endothelial inflammation via modulating SIRT1/AMPK axis', Biochemical Pharmacology, vol. 88, no. 2, pp. 189-200. https://doi.org/10.1016/j.bcp.2013.12.005

Aspirin attenuates vinorelbine-induced endothelial inflammation via modulating SIRT1/AMPK axis. / Tsai, Kun-Ling; Huang, Po Hsun; Kao, Chung Lan; Leu, Hsin Bang; Cheng, Yung Hsin; Liao, Yi Wen; Yang, Yi Ping; Chien, Yueh; Wang, Chien Ying; Hsiao, Chen Yuan; Chiou, Shih Hwa; Chen, Jaw Wen; Lin, Shing Jong.

In: Biochemical Pharmacology, Vol. 88, No. 2, 15.03.2014, p. 189-200.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Aspirin attenuates vinorelbine-induced endothelial inflammation via modulating SIRT1/AMPK axis

AU - Tsai, Kun-Ling

AU - Huang, Po Hsun

AU - Kao, Chung Lan

AU - Leu, Hsin Bang

AU - Cheng, Yung Hsin

AU - Liao, Yi Wen

AU - Yang, Yi Ping

AU - Chien, Yueh

AU - Wang, Chien Ying

AU - Hsiao, Chen Yuan

AU - Chiou, Shih Hwa

AU - Chen, Jaw Wen

AU - Lin, Shing Jong

PY - 2014/3/15

Y1 - 2014/3/15

N2 - Vinorelbine (VNR), a semisynthetic vinca alkaloid acquired from vinblastine, is frequently used as the candidate for intervention of solid tumors. Nevertheless, VNR-caused endothelial injuries may lead a mitigative effect of clinical treatment efficiency. A growing body of evidence reveals that aspirin is a potent antioxidant and anti-inflammation drug. We investigated whether aspirin attenuate VNR-induced endothelial dysfunction. Human endothelial cells (EA.hy 926) were treated with VNR to cause endothelial inflammation. Western blotting, ROS assay, ELISA were used to confirm the anti-inflammatory effect of aspirin. We confirmed that VNR supresses SIRT1 expression, reduced LKB1 and AMPK phosphorylation as well as enriched PKC activation in treated endothelial cells. Furthermore, the membrane translocation assay displayed that the levels of NADPH oxidase subunits p47phox and Rac-1 in membrane fractions of endothelial cells were higher in cells that had been treated with VNR for than in untreated cells. We corroborated that treatment of Aspirin significantly diminishes VNR-repressed SIRT1, LKB1 and AMPK phosphorylation and VNR-promoted NADPH oxidase activation, however, those findings were vanished by SIRT1 and AMPK siRNAs. Our data also shown that Aspirin represses VNR-activated TGF-beta-activated kinase-1 (TAK1) activation, inhibited the interaction of TAK1/TAK-binding protein1 (TAB1), suppressed NF-kappa B activation and pro-inflammatory cytokine secretion. We demonstrated a novel connection between VNR-caused oxidative damages and endothelial dysfunction, and provide further insight into the protective effects of aspirin in VNR-caused endothelial dysfunction.

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