Open Access

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
  • View Affiliations

  • 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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September 2019
Volume 20 Issue 3

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Copy and paste a formatted citation
APA
Lu, Z., Lu, C., Li, C., Jiao, Y., Li, Y., & Zhang, G. (2019). 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. Molecular Medicine Reports, 20, 2091-2100. https://doi.org/10.3892/mmr.2019.10474
MLA
Lu, Z., Lu, C., Li, C., Jiao, Y., Li, Y., Zhang, G."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". Molecular Medicine Reports 20.3 (2019): 2091-2100.
Chicago
Lu, Z., Lu, C., Li, C., Jiao, Y., Li, Y., Zhang, G."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". Molecular Medicine Reports 20, no. 3 (2019): 2091-2100. https://doi.org/10.3892/mmr.2019.10474