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Article

Direct interaction between caffeic acid phenethyl ester and human neutrophil elastase inhibits the growth and migration of PANC-1 cells

  • Authors:
    • Jianhui Duan
    • Yilixiati Xiaokaiti
    • Shengjun Fan
    • Yan Pan
    • Xin Li
    • Xuejun Li
  • View Affiliations / Copyright

    Affiliations: Department of Pharmacology, School of Basic Medical Sciences, Peking University and State Key Laboratory of Natural and Biomimetic Drugs, Peking University and Beijing Key Laboratory of Tumor Systems Biology, Peking University, Beijing 100191, P.R. China
  • Pages: 3019-3025
    |
    Published online on: March 21, 2017
       https://doi.org/10.3892/or.2017.5516
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Abstract

Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal malignant tumors of the digestive system, but the mechanisms of its development and progression are unclear. Inflammation is thought to be fundamental to pancreatic cancer development and caffeic acid phenethyl ester (CAPE) is an active component of honey bee resin or propolis with anti-inflammatory and anticancer activities. We investigated the inhibitory effects of CAPE on cell growth and migration induced by human neutrophil elastase (HNE) and report that HNE induced cancer cell migration at low doses and growth at higher doses. In contrast, lower CAPE doses inhibited migration and higher doses of CAPE inhibited the growth induced by HNE. HNE activity was significantly inhibited by CAPE (7.5-120 µM). Using quantitative real-time PCR and western blotting, we observed that CAPE (18-60 µM) did not affect transcription and translation of α1-antitrypsin (α1-AT), an endogenous HNE inhibitor. However, in an in silico drug target docking model, we found that CAPE directly bound to the binding pocket of HNE (25.66 kcal/mol) according to CDOCKER, and the residue of the catalytic site stabilized the interaction between CAPE and HNE as evidenced by molecular dynamic simulation. Response unit (RU) values of surface plasmon resonance (SPR) significantly increased with incremental CAPE doses (7.5-120 µM), indicating that CAPE could directly bind to HNE in a concentration-dependent manner. Thus, CAPE is an effective inhibitor of HNE via direct interaction whereby it inhibits the migration and growth of PANC-1 cells in a dose-dependent manner.
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Copy and paste a formatted citation
Spandidos Publications style
Duan J, Xiaokaiti Y, Fan S, Pan Y, Li X and Li X: Direct interaction between caffeic acid phenethyl ester and human neutrophil elastase inhibits the growth and migration of PANC-1 cells. Oncol Rep 37: 3019-3025, 2017.
APA
Duan, J., Xiaokaiti, Y., Fan, S., Pan, Y., Li, X., & Li, X. (2017). Direct interaction between caffeic acid phenethyl ester and human neutrophil elastase inhibits the growth and migration of PANC-1 cells. Oncology Reports, 37, 3019-3025. https://doi.org/10.3892/or.2017.5516
MLA
Duan, J., Xiaokaiti, Y., Fan, S., Pan, Y., Li, X., Li, X."Direct interaction between caffeic acid phenethyl ester and human neutrophil elastase inhibits the growth and migration of PANC-1 cells". Oncology Reports 37.5 (2017): 3019-3025.
Chicago
Duan, J., Xiaokaiti, Y., Fan, S., Pan, Y., Li, X., Li, X."Direct interaction between caffeic acid phenethyl ester and human neutrophil elastase inhibits the growth and migration of PANC-1 cells". Oncology Reports 37, no. 5 (2017): 3019-3025. https://doi.org/10.3892/or.2017.5516
Copy and paste a formatted citation
x
Spandidos Publications style
Duan J, Xiaokaiti Y, Fan S, Pan Y, Li X and Li X: Direct interaction between caffeic acid phenethyl ester and human neutrophil elastase inhibits the growth and migration of PANC-1 cells. Oncol Rep 37: 3019-3025, 2017.
APA
Duan, J., Xiaokaiti, Y., Fan, S., Pan, Y., Li, X., & Li, X. (2017). Direct interaction between caffeic acid phenethyl ester and human neutrophil elastase inhibits the growth and migration of PANC-1 cells. Oncology Reports, 37, 3019-3025. https://doi.org/10.3892/or.2017.5516
MLA
Duan, J., Xiaokaiti, Y., Fan, S., Pan, Y., Li, X., Li, X."Direct interaction between caffeic acid phenethyl ester and human neutrophil elastase inhibits the growth and migration of PANC-1 cells". Oncology Reports 37.5 (2017): 3019-3025.
Chicago
Duan, J., Xiaokaiti, Y., Fan, S., Pan, Y., Li, X., Li, X."Direct interaction between caffeic acid phenethyl ester and human neutrophil elastase inhibits the growth and migration of PANC-1 cells". Oncology Reports 37, no. 5 (2017): 3019-3025. https://doi.org/10.3892/or.2017.5516
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