Utilizing ethacrynic acid and ciclopirox olamine in liver cancer

Al‑Dali,Ahmad  M.; Weiher,Hans; Schmidt‑Wolf,Ingo  G.H.

doi:10.3892/ol.2018.9472

Utilizing ethacrynic acid and ciclopirox olamine in liver cancer

Authors:
- Ahmad M. Al‑Dali
- Hans Weiher
- Ingo G.H. Schmidt‑Wolf
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Affiliations: Center for Integrated Oncology, University Hospital Bonn, Bonn D‑53105, Germany, Department of Immunology and Cell Biology, Bonn‑Rhein‑Sieg University of Applied Sciences, Rheinbach D‑53359, Germany
Published online on: September 20, 2018 https://doi.org/10.3892/ol.2018.9472
Pages: 6854-6860

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Abstract

Once aberrantly activated, the Wnt/β‑catenin pathway may result in uncontrolled proliferation and eventually cancer. Efforts to counter and inhibit this pathway are mainly directed against β‑catenin, as it serves a role on the cytoplasm and the nucleus. In addition, specially‑generated lymphocytes are recruited for the purpose of treating liver cancer. Peripheral blood mononuclear lymphocytes are expanded by the timely addition of interferon γ, interleukin (IL)‑1β, IL‑2 and anti‑cluster of differentiation 3 antibody. The resulting cells are called cytokine‑induced killer (CIK) cells. The present study utilised these cells and combine them with drugs inhibiting the Wnt pathway in order to examine whether this resulted in an improvement in the killing ability of CIK cells against liver cancer cells. Drugs including ethacrynic acid (EA) and ciclopirox olamine (CPX) were determined to be suitable candidates, as determined by previous studies. Drugs were administered on their own and combined with CIK cells and then a cell viability assay was performed. These results suggest that EA‑treated cells demonstrated apoptosis and were significantly affected compared with untreated cells. Unlike EA, CPX killed normal and cancerous cells even at low concentrations. Subsequent to combining EA with CIK cells, the potency of killing was increased and a greater number of cells died, which proves a synergistic action. In summary, EA may be used as an anti‑hepatocellular carcinoma drug, while CPX possesses a high toxicity to cancerous as well as to normal cells. It was proposed that EA should be integrated into present therapeutic methods for cancer.

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