Auranofin induces urothelial carcinoma cell death via <br />reactive oxygen species production and synergy with cisplatin

Chen,San-Yuan; Chao,Chun-Nun; Huang,Hsin-Yi; Fang,Chiung-Yao

doi:10.3892/ol.2021.13179

Auranofin induces urothelial carcinoma cell death via
reactive oxygen species production and synergy with cisplatin

Authors:
- San-Yuan Chen
- Chun-Nun Chao
- Hsin-Yi Huang
- Chiung-Yao Fang
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Affiliations: Department of Chinese Medicine, Ditmanson Medical Foundation, Chiayi Christian Hospital, Chiayi 60002, Taiwan, R.O.C., Department of Pediatrics, Ditmanson Medical Foundation, Chiayi Christian Hospital, Chiayi 60002, Taiwan, R.O.C., Department of Medical Research, Ditmanson Medical Foundation, Chiayi Christian Hospital, Chiayi 60002, Taiwan, R.O.C.
Published online on: December 27, 2021 https://doi.org/10.3892/ol.2021.13179
Article Number: 61
Copyright: © Chen et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Urothelial carcinoma (UC) is one of the most common cancer types of the urinary tract. UC is associated with poor 5‑year survival rate, and resistance to cisplatin‑based therapy remains a challenge for invasive bladder cancer treatment. Therefore, there is an urgent need to develop new drugs for advanced UC therapy. Auranofin (AF) was developed over 30 years ago for the treatment of rheumatoid arthritis and has been reported to exert an antitumor effect by increasing the level of reactive oxygen species (ROS) in cancer cells. The aim of the present study was to examine the effects of AF on cancer cell proliferation, cell cycle and apoptosis, either alone or in combination with cisplatin. AF induced cell death in two separate cell lines, HT 1376 and BFTC 909, in a concentration‑ and time‑dependent manner by inducing cell cycle arrest. However, the distribution of cells in different phases of the cell cycle differed between the two cell lines, with G₀/G₁ cell cycle arrest in HT 1376 cells and S phase arrest in BFTC 909 cells. In addition, AF induced apoptosis in HT 1376, as well as redox imbalance in both HT 1376 and BFTC 909 cells. Cell viability was rescued following treatment with N‑acetyl‑L‑cysteine, a ROS scavenger. Furthermore, AF treatment synergistically increased the cytotoxicity of HT 1376 and BFTC 909 cells when combined with cisplatin treatment. These findings suggest that AF may represent a potential candidate drug against UC and increase the therapeutic effect of cisplatin.

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