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

Cao,Yan; Yin,Xiang; Jia,Yiping; Liu,Bingyan; Wu,Shaoqiu; Shang,Mingyi

doi:10.3892/ijmm.2018.3722

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
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Affiliations: Department of Interventional Radiology, Tongren Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200336, P.R. China
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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