Auranofin inhibits the proliferation of lung cancer cells via necrosis and caspase‑dependent apoptosis

Cui,Xia Ying; Park,Sun Hyang; Park,Woo Hyun

doi:10.3892/or.2020.7818

Auranofin inhibits the proliferation of lung cancer cells via necrosis and caspase‑dependent apoptosis

Authors:
- Xia Ying Cui
- Sun Hyang Park
- Woo Hyun Park
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Affiliations: Department of Physiology, Medical School, Research Institute for Endocrine Sciences, Jeonbuk National University, Jeonju, Jeollabuk 54907, Republic of Korea
Published online on: October 21, 2020 https://doi.org/10.3892/or.2020.7818
Pages: 2715-2724

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Abstract

Auranofin, an inhibitor of thioredoxin reductase (TrxR), inhibits the growth of a variety of cancer cells. In the present study, various lung cancer cells were used to investigate the molecular basis of anti‑cancer effects of auranofin, including cell death via apoptosis or necrosis and cell cycle arrest. Generally, auranofin inhibited the growth of the tested lung cancer cell lines in a dose‑dependent manner with an IC50 of 3‑4 µM at 24 h. This agent significantly decreased the activity of TrxR in Calu‑6 and A549 lung cancer cells. In addition, auranofin (3‑5 µM) triggered necrosis in lung cancer cells measured by the release of lactate dehydrogenase (LDH) into culture media. Auranofin increased the percentages of sub‑G1 cells in Calu‑6 and A549 cells. DNA flow cytometry showed that auranofin induced G2/M phase arrest of Calu‑6 cells. This agent also efficiently induced apoptosis, accompanied by loss of mitochondrial membrane potential (MMP; ∆Ψm), increases in cleavage forms of caspase‑3 and poly (ADP‑ribose) polymerase (PARP), and a high ratio of BAX to Bcl‑2 proteins. Furthermore, various caspase inhibitors reduced apoptosis and MMP (∆Ψm) loss in auranofin‑treated Calu‑6 cells. In particular, the pan‑caspase inhibitor, benzyloxycarbonyl‑Val‑Ala‑Asp‑fluoromethylketone (Z‑VAD), decreased cleavage forms of caspase‑3, ‑8, and ‑9 in these cells. In conclusion, auranofin inhibited the proliferation of lung cancer cells, especially Calu‑6 cells, via cell cycle arrest and cell death due to necrosis or caspase‑dependent apoptosis.

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