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Nutr Res. 2018 Jul 21. pii: S0271-5317(18)30132-5. doi: 10.1016/j.nutres.2018.07.010. [Epub ahead of print]

Lycopene treatment inhibits activation of Jak1/Stat3 and Wnt/β-catenin signaling and attenuates hyperproliferation in gastric epithelial cells.

Author information

1
Department of Food and Nutrition, Brain Korea 21 PLUS Project, College of Human Ecology, Yonsei University, Seoul 03722, Korea. Electronic address: bohye0411@gmail.com.
2
Department of Food and Nutrition, Brain Korea 21 PLUS Project, College of Human Ecology, Yonsei University, Seoul 03722, Korea. Electronic address: jwlim11@yonsei.ac.kr.
3
Department of Food and Nutrition, Brain Korea 21 PLUS Project, College of Human Ecology, Yonsei University, Seoul 03722, Korea. Electronic address: kim626@yonsei.ac.kr.

Abstract

Helicobacter pylori (H pylori) colonizes the human stomach and increases the risk of gastric diseases including gastric cancer. H pylori increases reactive oxygen species (ROS), which activate Janus-activator kinase 1 (Jak1)/signal transducers and activators of transcription 3 (Stat3) in gastric epithelial cells. ROS mediate hyperproliferation, a hallmark of carcinogenesis, by activating Wnt/β-catenin signaling in various cells. Lycopene is a potent antioxidant exhibiting anticancer effects. We hypothesized that lycopene may inhibit H pylori-induced hyperproliferation by suppressing ROS-mediated activation of Jak1/Stat3 and Wnt/β-catenin signaling, and β-catenin target gene expression in gastric epithelial cells. We determined cell viability, ROS levels, and the protein levels of phospho- and total Jak1/Stat3, Wnt/β-catenin signaling molecules, Wnt-1, lipoprotein-related protein 5, and β-catenin target oncogenes (c-Myc and cyclin E) in H pylori-infected gastric epithelial AGS cells. The Jak1/Stat3 inhibitor AG490 served as the control treatment. The significance of the differences among groups was calculated using the 1-way analysis of variance followed by Newman-Keuls post hoc tests. The results show that lycopene reduced ROS levels and inhibited Jak1/Stat3 activation, alteration of Wnt/β-catenin multiprotein complex molecules, expression of c-Myc and cyclin E, and cell proliferation in H pylori-infected AGS cells. AG490 similarly inhibited H pylori-induced cell proliferation, alteration of Wnt/β-catenin multiprotein complex molecules, and oncogene expression. H pylori increased the levels of Wnt-1 and its receptor lipoprotein-related protein 5; this increase was inhibited by either lycopene or AG490 in AGS cells. In conclusion, lycopene inhibits ROS-mediated activation of Jak1/Stat3 and Wnt/β-catenin signaling and, thus, oncogene expression in relation to hyperproliferation in H pylori-infected gastric epithelial cells. Lycopene might be a potential and promising nutrient for preventing H pylori-associated gastric diseases including gastric cancer.

KEYWORDS:

Helicobacter pylori; Jak1; Lycopene; Stat3; Wnt; β-Catenin

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