Plumbagin, a natural naphthoquinone, inhibits the growth of esophageal squamous cell carcinoma cells through inactivation of STAT3

  • Authors:
    • Yan Cao
    • Xiang Yin
    • Yiping Jia
    • Bingyan Liu
    • Shaoqiu Wu
    • Mingyi Shang
  • View Affiliations

  • Published online on: June 7, 2018     https://doi.org/10.3892/ijmm.2018.3722
  • Pages: 1569-1576
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Abstract

Although plumbagin, a natural naphthoquinone, has exhibited antiproliferative activity in numerous types of cancer, its anticancer potential in esophageal squamous cell carcinoma (ESCC) remains unclear. In the present study, the effect of plumbagin on the growth of ESCC cells was investigated in vitro and in vivo. ESCC cells were treated with plumbagin and tested for cell cycle distribution and apoptosis. The involvement of STAT3 signaling in the effect of plumbagin was examined. The results demonstrated that plumbagin treatment suppressed ESCC cell viability and proliferation, yet normal esophageal epithelial cell viability was not affected. Plumbagin treatment increased the proportion of cells in the G0/G1 phase of the cell cycle and decreased the proportion of cells in the S phase. Furthermore, plumbagin‑treated ESCC cells displayed a significantly greater % of apoptotic cells. Western blot analysis confirmed that plumbagin upregulated tumor protein p53 and cyclin‑dependent kinase inhibitor 1A (also known as p21), while it downregulated cyclin D1, cyclin‑dependent kinase 4, and induced myeloid leukemia cell differentiation protein Mcl‑1. Mechanistically, plumbagin inhibited STAT3 activation, and overexpression of constitutively active STAT3 reversed the plumbagin‑mediated growth suppression in ESCC cells. In vivo studies demonstrated that plumbagin delayed the growth of ESCC xenograft tumors and reduced STAT3 phosphorylation. Overall, plumbagin was demonstrated to target STAT3 signaling and to inhibit the growth of ESCC cells both in vitro and in vivo, suggesting that it may represent a potential anticancer agent for ESCC.

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September 2018
Volume 42 Issue 3

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Online ISSN:1791-244X

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Copy and paste a formatted citation
APA
Cao, Y., Yin, X., Jia, Y., Liu, B., Wu, S., & Shang, M. (2018). Plumbagin, a natural naphthoquinone, inhibits the growth of esophageal squamous cell carcinoma cells through inactivation of STAT3. International Journal of Molecular Medicine, 42, 1569-1576. https://doi.org/10.3892/ijmm.2018.3722
MLA
Cao, Y., Yin, X., Jia, Y., Liu, B., Wu, S., Shang, M."Plumbagin, a natural naphthoquinone, inhibits the growth of esophageal squamous cell carcinoma cells through inactivation of STAT3". International Journal of Molecular Medicine 42.3 (2018): 1569-1576.
Chicago
Cao, Y., Yin, X., Jia, Y., Liu, B., Wu, S., Shang, M."Plumbagin, a natural naphthoquinone, inhibits the growth of esophageal squamous cell carcinoma cells through inactivation of STAT3". International Journal of Molecular Medicine 42, no. 3 (2018): 1569-1576. https://doi.org/10.3892/ijmm.2018.3722