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J Exp Clin Cancer Res. 2018 Dec 5;37(1):303. doi: 10.1186/s13046-018-0959-0.

The natural polyphenol curcumin induces apoptosis by suppressing STAT3 signaling in esophageal squamous cell carcinoma.

Liu Y1,2,3, Wang X4, Zeng S1,2, Zhang X1,2, Zhao J1,2, Zhang X1,2, Chen X1,2, Yang W1,2, Yang Y5, Dong Z1,2, Zhu J6, Xu X7,8, Tian F9,10.

Author information

1
Department of Pathophysiology, School of Basic Medical Sciences, Zhengzhou University, Zhengzhou, Henan, 450001, People's Republic of China.
2
Henan Provincial Cooperative Innovation Center for Cancer Chemoprevention, Zhengzhou, Henan, 450001, People's Republic of China.
3
Clinical Research Center, People's Hospital of Zhengzhou, Zhengzhou, Henan, 450001, People's Republic of China.
4
Department of Histology and Embryology, School of Basic Medical Sciences, Zhengzhou University, Zhengzhou, Henan, 450001, People's Republic of China.
5
Suzhou Institute of Systems Medicine, Center for Systems Medicine, Chinese Academy of Medical Sciences, Suzhou, Jiangsu, 215123, People's Republic of China.
6
School of Medicine and Pharmaceutics, Jiangnan University, Wuxi, Jiangsu, 214000, People's Republic of China.
7
Department of Pathophysiology, School of Basic Medical Sciences, Zhengzhou University, Zhengzhou, Henan, 450001, People's Republic of China. zitanxu@163.com.
8
Suzhou Institute of Systems Medicine, Center for Systems Medicine, Chinese Academy of Medical Sciences, Suzhou, Jiangsu, 215123, People's Republic of China. zitanxu@163.com.
9
Department of Pathophysiology, School of Basic Medical Sciences, Zhengzhou University, Zhengzhou, Henan, 450001, People's Republic of China. tianfang418@163.com.
10
Henan Provincial Cooperative Innovation Center for Cancer Chemoprevention, Zhengzhou, Henan, 450001, People's Republic of China. tianfang418@163.com.

Abstract

BACKGROUND:

We and others have previously shown that the STAT3 signaling pathway is activated in some esophageal squamous cell carcinoma (ESCC) cells and is required for the survival and growth of these primary ESCC-derived xenografts. It has also been shown that the natural polyphenol curcumin is an effective anti-tumor agent.

METHODS:

Luciferase assay and immunoblotting were performed to examine whether curcumin suppressed STAT3 signaling. CCK-8 assay and xenografts were utilized for analyzing ESCC cell growth in culture and mice. Soft agar assay was carried out to determine the colony formation ability of ESCC cells in the presence or absence of curcumin. Cell death and cell cycle were assessed by In CELL Analyzer 2000. Immunohistochemistry and TUNEL assay were used for detecting apoptosis in ESCC tisuses. Molecular docking was performed to evaluate the interaction of curcumin with JAK2. JAK2 activity was assessed using an in vitro cell-free system. HE staining was used to evaluate the ESCC tissues.

RESULTS:

The natural polyphenol curcumin inhibited STAT3 phosphorylation rapidly and blocked STAT3-mediated signaling in ESCC cells. It also induced growth arrest and apoptosis in cultured ESCC cells, which were attenuated by enforced expression of STAT3. Furthermore, curcumin preferentially blocked the growth of primary ESCC-derived xenografts that harbored activated STAT3.

CONCLUSIONS:

Curcumin is able to exert anti-tumor action through inhibiting the STAT3 signaling pathway. Giving its wide use in traditional medicines with low toxicity and few adverse reactions, it is conceivable that curcumin might be further explored as a unique STAT3 inhibitor for anti-cancer therapies.

KEYWORDS:

Apoptosis; Curcumin; Esophageal squamous cell carcinoma; PDX model; STAT3

PMID:
30518397
PMCID:
PMC6280482
DOI:
10.1186/s13046-018-0959-0
[Indexed for MEDLINE]
Free PMC Article

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