Dracorhodin perchlorate induces apoptosis and G2/M cell cycle arrest in human esophageal squamous cell carcinoma through inhibition of the JAK2/STAT3 and AKT/FOXO3a pathways

Lu,Zhengyang; Lu,Chenyang; Li,Cheng; Jiao,Yan; Li,Yanqing; Zhang,Guangxin

doi:10.3892/mmr.2019.10474

Dracorhodin perchlorate induces apoptosis and G2/M cell cycle arrest in human esophageal squamous cell carcinoma through inhibition of the JAK2/STAT3 and AKT/FOXO3a pathways

Authors:
- Zhengyang Lu
- Chenyang Lu
- Cheng Li
- Yan Jiao
- Yanqing Li
- Guangxin Zhang
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Affiliations: Department of General Surgery, The Second Hospital of Jilin University, Changchun, Jilin 130041, P.R. China, Department of Respiratory Medicine, Third Hospital of Xi'an, Xi'an, Shaanxi 710082, P.R. China, Department of Cardiovascular Medicine, The First Hospital of Jilin University, Changchun, Jilin 130021, P.R. China, Department of Hepatobiliary and Pancreatic Surgery, The First Hospital of Jilin University, Changchun, Jilin 130021, P.R. China, Department of Pathophysiology, College of Basic Medical Sciences, Jilin University, Changchun, Jilin 130021, P.R. China, Department of Thoracic Surgery, The Second Hospital of Jilin University, Changchun, Jilin 130041, P.R. China
Published online on: July 8, 2019 https://doi.org/10.3892/mmr.2019.10474
Pages: 2091-2100
Copyright: © Lu et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Dracorhodin perchlorate (DP), a synthetic analogue of the anthocyanin red pigment dracorhodin, has been shown to exert various pharmacological effects, including anticancer activity. However, its effects on human esophageal squamous cell carcinoma (ESCC) cells have not been previously investigated, and the molecular mechanisms underlying its anticancer activity remain unclear. In the present study, it was demonstrated that DP significantly reduced the viability of ESCC cells compared with that noted in normal human liver LO2 cells. Treatment with DP induced G2/M phase cell cycle arrest through upregulation of p21 and p27, and downregulation of cyclin B1 and Cdc2. Furthermore, DP treatment induced caspase‑dependent apoptosis, which could be reversed by exposure to Z‑VAD‑FMK, a caspase inhibitor. Western blotting demonstrated that DP induced apoptosis through extrinsic and intrinsic pathways by upregulating death receptor 4 (DR4), DR5, cleaved caspase‑3/‑7/‑9 and cleaved poly (ADP‑ribose) polymerase (PARP), and by decreasing total PARP, total caspase‑3/7, Bcl‑2 and caspase‑9/‑10. Moreover, DP treatment decreased the phosphorylation of Janus kinase 2 (JAK2), signal transducer and activator of transcription 3 (STAT3), AKT, and forkhead box O3a (FOXO3a) in ESCC cells, indicating that the activity of the JAK2/STAT3 and AKT/FOXO3a signaling pathways was inhibited. Therefore, DP is a promising therapeutic agent for ESCC.

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