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

Bohye Park, Joo Weon Lim, Hyeyoung Kim

Research output: Contribution to journalArticlepeer-review

12 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)70-81
Number of pages12
JournalNutrition Research
Volume70
DOIs
Publication statusPublished - 2019 Oct

Bibliographical note

Funding Information:
Part of this study was presented at the 2017 Korean Nutrition Society 50th Anniversary International Conference, November 2-3, 2017, in Seoul, Korea.This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors. Part of this manuscript was presented at the Joint Conference of the Society for Free Radical Research and the Society of Nutrition and Food Science, University of Hohenheim, Stuttgart, Germany (Sept. 2-4, 2015). The abstract of the presentation was published in Free Radical Biology and Medicine 86; S21, 2015. Bohye Park performed the experiments, researched data, and drafted the manuscript. Hyeyoung Kim provided experimental concepts and design, and edited the manuscript. Joo Weon Lim contributed to analysis tools; all authors read and approved the final manuscript. The authors declare no conflict of interest.

Publisher Copyright:
© 2018 Elsevier Inc.

All Science Journal Classification (ASJC) codes

  • Endocrinology, Diabetes and Metabolism
  • Endocrinology
  • Nutrition and Dietetics

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