Vinorelbine-Induced Oxidative Injury in Human Endothelial Cells Mediated by AMPK/PKC/NADPH/NF-κB Pathways

Kun Ling Tsai, Tsan Hung Chiu, Mei Hsueh Tsai, Hsiao Yun Chen, Hsiu Chung Ou

研究成果: Article同行評審

18 引文 斯高帕斯(Scopus)


Vinorelbine tartrate (VNR), a semi-synthetic vinca alkaloid acquired from vinblastine, has extensively been used as an anticancer agent. However, VNR-induced oxidative damage may cause several side effects, such as venous irritation, vascular pain, and necrotizing vasculitis, thereby repressing clinical treatment efficiency. The molecular mechanisms underlying the induced oxidative stress in endothelial cells are still largely unknown. This study was designed to test the hypothesis that VNR induces oxidative injury through modulation of AMP-activated protein kinase (AMPK) and possible mechanisms were then explored. Human umbilical vein endothelial cells (HUVECs) were treated with VNR (5-0.625 μM) to produce oxidative damage. The VNR-mediated AMPK, PKC, and NADPH oxidase expressions were investigated by western blotting. Furthermore, several oxidative stress-induced oxidative damage markers as well as pro-inflammatory responses were also investigated. VNR treatment resulted in dephosphorylation of AMPK, which in turn led to an activation of NADPH oxidase by PKC; however, the phenomena were repressed by AICAR (an agonist of AMPK). Furthermore, VNR suppressed Akt/eNOS and enhanced p38 mitogen-activated protein kinase (MAPK), which in turn activated the NF-κB pathway. Furthermore, VNR facilitated several pro-inflammatory events, such as the adherence of monocytic THP-1 cells to HUVECs, pro-inflammatory cytokines release, and overexpression of adhesion molecular. Our results highlight a possible molecular mechanism for VNR-mediated endothelial dysfunction.

頁(從 - 到)467-479
期刊Cell Biochemistry and Biophysics
出版狀態Published - 2012 四月

All Science Journal Classification (ASJC) codes

  • 生物物理學
  • 生物化學
  • 細胞生物學


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