Rebamipide attenuates Helicobacter pylori CagA-induced self-renewal capacity via modulation of β-catenin signaling axis in gastric cancer-initiating cells

Dong Woo Kang; Yu Na Noh; Won Chan Hwang; Kang Yell Choi; Do Sik Min

doi:10.1016/j.bcp.2016.06.003

Rebamipide attenuates Helicobacter pylori CagA-induced self-renewal capacity via modulation of β-catenin signaling axis in gastric cancer-initiating cells

Dong Woo Kang, Yu Na Noh, Won Chan Hwang, Kang Yell Choi, Do Sik Min

Research output: Contribution to journal › Article › peer-review

9 Citations (Scopus)

Abstract

Rebamipide, a mucosal-protective agent, is used clinically for treatment of gastritis and peptic ulcers induced by Helicobacter pylori (H. pylori) which is associated with increased risk of gastric cancer. Although rebamipide is known to inhibit the growth of gastric cancer cells, the action mechanisms of rebamipide in gastric carcinogenesis remains elusive. Here, we show that rebamipide suppresses H. pylori CagA-induced β-catenin and its target cancer-initiating cells (C-IC) marker gene expression via upregulation of miRNA-320a and -4496. Rebamipide attenuated in vitro self-renewal capacity of H. pylori CagA-infected gastric C-IC via modulation of miRNA-320a/-4496-β-catenin signaling axis. Moreover, rebamipide enhanced sensitivity to chemotherapeutic drugs in CagA-expressed gastric C-IC. Furthermore, rebamipide suppressed tumor-initiating capacity of gastric C-IC, probably via suppression of CagA-induced C-IC properties. These data provide novel insights for the efficacy of rebamipide as a chemoprotective drug against H. pylori CagA-induced carcinogenic potential.

Original language	English
Pages (from-to)	36-44
Number of pages	9
Journal	Biochemical Pharmacology
Volume	113
DOIs	https://doi.org/10.1016/j.bcp.2016.06.003
Publication status	Published - 2016 Aug 1

Bibliographical note

Funding Information:
This work was supported by grant from National Research Foundation of Korea (NRF), NRF-2015R1A2A1A05001884 , the Translational Research Center for Protein Function Control ( 2016R1A5A11004694 ), and a National R&D Program for Cancer Control grant from the Ministry for Health, Welfare, and Family Affairs (Republic of Korea; 0920050 ). The authors have no competing financial interests related to this study.

Publisher Copyright:
© 2016 Elsevier Inc.

All Science Journal Classification (ASJC) codes

Biochemistry
Pharmacology

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This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1016/j.bcp.2016.06.003

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title = "Rebamipide attenuates Helicobacter pylori CagA-induced self-renewal capacity via modulation of β-catenin signaling axis in gastric cancer-initiating cells",

abstract = "Rebamipide, a mucosal-protective agent, is used clinically for treatment of gastritis and peptic ulcers induced by Helicobacter pylori (H. pylori) which is associated with increased risk of gastric cancer. Although rebamipide is known to inhibit the growth of gastric cancer cells, the action mechanisms of rebamipide in gastric carcinogenesis remains elusive. Here, we show that rebamipide suppresses H. pylori CagA-induced β-catenin and its target cancer-initiating cells (C-IC) marker gene expression via upregulation of miRNA-320a and -4496. Rebamipide attenuated in vitro self-renewal capacity of H. pylori CagA-infected gastric C-IC via modulation of miRNA-320a/-4496-β-catenin signaling axis. Moreover, rebamipide enhanced sensitivity to chemotherapeutic drugs in CagA-expressed gastric C-IC. Furthermore, rebamipide suppressed tumor-initiating capacity of gastric C-IC, probably via suppression of CagA-induced C-IC properties. These data provide novel insights for the efficacy of rebamipide as a chemoprotective drug against H. pylori CagA-induced carcinogenic potential.",

author = "Kang, {Dong Woo} and Noh, {Yu Na} and Hwang, {Won Chan} and Choi, {Kang Yell} and Min, {Do Sik}",

note = "Funding Information: This work was supported by grant from National Research Foundation of Korea (NRF), NRF-2015R1A2A1A05001884 , the Translational Research Center for Protein Function Control ( 2016R1A5A11004694 ), and a National R&D Program for Cancer Control grant from the Ministry for Health, Welfare, and Family Affairs (Republic of Korea; 0920050 ). The authors have no competing financial interests related to this study. Publisher Copyright: {\textcopyright} 2016 Elsevier Inc.",

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AU - Choi, Kang Yell

AU - Min, Do Sik

N1 - Funding Information: This work was supported by grant from National Research Foundation of Korea (NRF), NRF-2015R1A2A1A05001884 , the Translational Research Center for Protein Function Control ( 2016R1A5A11004694 ), and a National R&D Program for Cancer Control grant from the Ministry for Health, Welfare, and Family Affairs (Republic of Korea; 0920050 ). The authors have no competing financial interests related to this study. Publisher Copyright: © 2016 Elsevier Inc.

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N2 - Rebamipide, a mucosal-protective agent, is used clinically for treatment of gastritis and peptic ulcers induced by Helicobacter pylori (H. pylori) which is associated with increased risk of gastric cancer. Although rebamipide is known to inhibit the growth of gastric cancer cells, the action mechanisms of rebamipide in gastric carcinogenesis remains elusive. Here, we show that rebamipide suppresses H. pylori CagA-induced β-catenin and its target cancer-initiating cells (C-IC) marker gene expression via upregulation of miRNA-320a and -4496. Rebamipide attenuated in vitro self-renewal capacity of H. pylori CagA-infected gastric C-IC via modulation of miRNA-320a/-4496-β-catenin signaling axis. Moreover, rebamipide enhanced sensitivity to chemotherapeutic drugs in CagA-expressed gastric C-IC. Furthermore, rebamipide suppressed tumor-initiating capacity of gastric C-IC, probably via suppression of CagA-induced C-IC properties. These data provide novel insights for the efficacy of rebamipide as a chemoprotective drug against H. pylori CagA-induced carcinogenic potential.

AB - Rebamipide, a mucosal-protective agent, is used clinically for treatment of gastritis and peptic ulcers induced by Helicobacter pylori (H. pylori) which is associated with increased risk of gastric cancer. Although rebamipide is known to inhibit the growth of gastric cancer cells, the action mechanisms of rebamipide in gastric carcinogenesis remains elusive. Here, we show that rebamipide suppresses H. pylori CagA-induced β-catenin and its target cancer-initiating cells (C-IC) marker gene expression via upregulation of miRNA-320a and -4496. Rebamipide attenuated in vitro self-renewal capacity of H. pylori CagA-infected gastric C-IC via modulation of miRNA-320a/-4496-β-catenin signaling axis. Moreover, rebamipide enhanced sensitivity to chemotherapeutic drugs in CagA-expressed gastric C-IC. Furthermore, rebamipide suppressed tumor-initiating capacity of gastric C-IC, probably via suppression of CagA-induced C-IC properties. These data provide novel insights for the efficacy of rebamipide as a chemoprotective drug against H. pylori CagA-induced carcinogenic potential.

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Rebamipide attenuates Helicobacter pylori CagA-induced self-renewal capacity via modulation of β-catenin signaling axis in gastric cancer-initiating cells

Abstract

Bibliographical note

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