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World J Gastroenterol. 2017 Apr 14;23(14):2511-2518. doi: 10.3748/wjg.v23.i14.2511.

Berberine displays antitumor activity in esophageal cancer cells in vitro.

Author information

1
Shu-Xian Jiang, Bo Qi, Wen-Jian Yao, Cheng-Wei Gu, Xiu-Feng Wei, Yi Zhao, Yu-Zhen Liu, Bao-Sheng Zhao, Department of Thoracic Surgery, The First Affiliated Hospital of Xinxiang Medical University, Weihui 453100, Henan Province, China.

Abstract

AIM:

To investigate the effects of berberine on esophageal cancer (EC) cells and its molecular mechanisms.

METHODS:

Human esophageal squamous cell carcinoma cell line KYSE-70 and esophageal adenocarcinoma cell line SKGT4 were used. The effects of berberine on cell proliferation were evaluated using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. For cell cycle progression, KYSE-70 cells were stained with propidium iodide (PI) staining buffer (10 mg/mL PI and 100 mg/mL RNase A) for 30 min and cell cycle was analyzed using a BD FACSCalibur flow cytometer. For apoptosis assay, cells were stained with an Annexin V-FITC/PI apoptosis detection kit. The rate of apoptotic cells was analyzed using a dual laser flow cytometer and estimated using BD ModFit software. Levels of proteins related to cell cycle and apoptosis were examined by western blotting.

RESULTS:

Berberine treatment resulted in growth inhibition of KYSE-70 and SKGT4 cells in a dose-dependent and time-dependent manner. KYSE-70 cells were more susceptible to the inhibitory activities of berberine than SKGT4 cells were. In KYSE-70 cells treated with 50 μmol/L berberine for 48 h, the number of cells in G2/M phase (25.94% ± 5.01%) was significantly higher than that in the control group (9.77% ± 1.28%, P < 0.01), and berberine treatment resulted in p21 up-regulation in KYSE-70 cells. Flow cytometric analyses showed that berberine significantly augmented the KYSE-70 apoptotic population at 12 and 24 h post-treatment, when compared with control cells (0.83% vs 43.78% at 12 h, P < 0.05; 0.15% vs 81.86% at 24 h, P < 0.01), and berberine-induced apoptotic effect was stronger at 24 h compared with 12 h. Western blotting showed that berberine inhibited the phosphorylation of Akt, mammalian target of rapamycin and p70S6K, and enhanced AMP-activated protein kinase phosphorylation in a sustained manner.

CONCLUSION:

Berberine is an inhibitor of human EC cell growth and could be considered as a potential drug for the treatment of EC patients.

KEYWORDS:

Antitumor activity; Apoptosis; Berberine; Cell cycle; Esophageal cancer; Proliferation

PMID:
28465635
PMCID:
PMC5394514
DOI:
10.3748/wjg.v23.i14.2511
[Indexed for MEDLINE]
Free PMC Article

Conflict of interest statement

Conflict-of-interest statement: The authors declare that no conflict of interest exists in this study.

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