A novel antitumor dithiocarbamate compound inhibits the EGFR/AKT signaling pathway and induces apoptosis in esophageal cancer cells

Yang,Yun; Tian,Ziyin; Zhao,Xinghua; Li,Ya; Duan,Shuyan

doi:10.3892/ol.2020.11638

A novel antitumor dithiocarbamate compound inhibits the EGFR/AKT signaling pathway and induces apoptosis in esophageal cancer cells

Authors:
- Yun Yang
- Ziyin Tian
- Xinghua Zhao
- Ya Li
- Shuyan Duan
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Affiliations: Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Xinxiang Medical University, Xinxiang, Henan 453000, P.R. China, Department of Gastroenterology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450000, P.R. China
Published online on: May 18, 2020 https://doi.org/10.3892/ol.2020.11638
Pages: 877-883
Copyright: © Yang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Dithiocarbamate has been reported to possess a potent antitumor efficacy against several types of cancer, such as ovarian cancer, breast cancer and hepatocellular carcinoma; however, only a few studies have investigated its inhibitory effect on esophageal cancer. Dipyridylhydrazone dithiocarbamate (DpdtC) is a novel dithiocarbamate derivative that was recently designed, synthesized and evaluated in our previous study. In the present study, the cell growth inhibition and apoptosis induced by DpdtC were measured using the CCK‑8 and Annexin V‑FITC/propidium iodide staining assays, respectively. Epidermal growth factor receptor (EGFR) signaling pathway and apoptosis related protein levels were examined by western blotting. In vivo effect of DpdtC was evaluated in nude mice bearing KYSE‑450 xenograft tumors. The aims of the present study were to further evaluate the antitumor effects of DpdtC on esophageal cancer cells (KYSE‑150 and KYSE‑450 cells), and to investigate its potential mechanism of action in vitro and in vivo. It was found that DpdtC significantly inhibited KYSE‑150 and KYSE‑450 cell proliferation by regulating the EGFR/AKT signaling pathway and inducing apoptosis. In addition, this effect was further identified in vivo; DpdtC inhibited the growth of the KYSE‑450 esophageal cancer xenografts by regulating the EGFR/AKT signaling pathway. Furthermore, DpdtC did not affect the body weight in mice. Collectively, the present results suggested that DpdtC may be a promising antitumor drug candidate for the treatment of esophageal cancer.

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