Quinalizarin induces ROS‑mediated apoptosis via the MAPK, STAT3 and NF‑κB signaling pathways in human breast cancer cells

Zang,Yan‑Qing; Feng,Yan‑Yu; Luo,Ying‑Hua; Zhai,Yu‑Qing; Ju,Xue‑Ying; Feng,Yu‑Chao; Sheng,Ya‑Nan; Wang,Jia‑Ru; Yu,Chang‑Qing; Jin,Cheng‑Hao

doi:10.3892/mmr.2019.10725

Quinalizarin induces ROS‑mediated apoptosis via the MAPK, STAT3 and NF‑κB signaling pathways in human breast cancer cells

Authors:
- Yan‑Qing Zang
- Yan‑Yu Feng
- Ying‑Hua Luo
- Yu‑Qing Zhai
- Xue‑Ying Ju
- Yu‑Chao Feng
- Ya‑Nan Sheng
- Jia‑Ru Wang
- Chang‑Qing Yu
- Cheng‑Hao Jin
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Affiliations: Department of Food Science and Engineering, College of Food Science, Heilongjiang Bayi Agricultural University, Daqing, Heilongjiang 163319, P.R. China, Department of Grass Science, College of Animal Science and Veterinary Medicine, Heilongjiang Bayi Agricultural University, Daqing, Heilongjiang 163319, P.R. China, Department of Biochemistry and Molecular Biology, College of Life Science and Technology, Heilongjiang Bayi Agricultural University, Daqing, Heilongjiang 163319, P.R. China
Published online on: October 2, 2019 https://doi.org/10.3892/mmr.2019.10725
Pages: 4576-4586
Copyright: © Zang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Quinalizarin has been demonstrated to exhibit potent antitumor activities in lung cancer and gastric cancer cells, but currently, little is known regarding its anticancer mechanisms in human breast cancer cells. The aim of the present study was to investigate the apoptotic effects of quinalizarin in MCF‑7 cells and to analyze its molecular mechanisms. The MTT assay was used to evaluate the viability of human breast cancer cells that had been treated with quinalizarin and 5‑fluorouracil. Flow cytometric analyses and western blotting were used to investigate the effects of quinalizarin on apoptosis and cycle arrest in MCF‑7 cells with focus on reactive oxygen species (ROS) production. The results demonstrated that quinalizarin exhibited significant cytotoxic effects on human breast cancer cells in a dose‑dependent manner. Accompanying ROS, quinalizarin induced MCF‑7 cell mitochondrial‑associated apoptosis by regulating mitochondrial‑associated apoptosis, and caused cell cycle arrest at the G2/M phase in a time‑dependent manner. Furthermore, quinalizarin can activate p38 kinase and JNK, and inhibit the extracellular signal‑regulated kinase, signal transducer and activator of transcription 3 (STAT3) and NF‑κB signaling pathways. These effects were blocked by mitogen‑activated protein kinase (MAPK) inhibitor and N‑acetyl‑L‑cysteine. The results from the present study suggested that quinalizarin induced G2/M phase cell cycle arrest and apoptosis in MCF‑7 cells through ROS‑mediated MAPK, STAT3 and NF‑κB signaling pathways. Thus, quinalizarin may be useful for human breast cancer treatment, as well as the treatment of other cancer types.

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