Cite this article
54
Download
456
Views
Journal Browser
Volume | Year
Issue
Search
News and Announcements
View All
ORIGINAL RESEARCH ARTICLE

Emodin Suppresses Helicobacter pylori- Induced Gastric Carcinogenesis in GES-1 Cells by Regulating the PI3K/AKT and Nrf2 Signaling Pathways

Palanimuthu Duraisami1 Rajasekar Muthusamy2*
Show Less
1 Department of Biotechnology, Bharathidasan University, Thirucharapalli, Tamil Nadu-620024, India
2 Department of Biochemistry and Biotechnology, Annamalai University, Annamalainagar-608002, Tamil Nadu, India
CP 2023, 5(3), 2582
Submitted: 5 May 2023 | Accepted: 30 June 2023 | Published: 16 July 2023
© 2023 by the Author(s). This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution 4.0 International License ( https://creativecommons.org/licenses/by/4.0/ )
Abstract

Helicobacter pylori (H. pylori) is recognized as a microbial carcinogen among gram-negative bacteria and is considered the most significant risk factor for the development of human gastric cancer. Consequently, inhibiting the growth of H. pylori has become a critical strategy for preventing gastric cancer. This study focuses on the inhibitory effects of emodin (EDN) against H. pylori-induced gastric carcinogenic signaling in human gastric epithelial cells (GES-1). In vitro cytotoxicity assessments revealed that a concentration of 40 µM of EDN provided remarkable protection to gastric cells, resulting in 85% cell viability without inducing toxicity. Furthermore, EDN prevented the H. pylori-induced depletion of antioxidants, which was mediated by reactive oxygen species (ROS) generation, DNA damage, and nuclear fragmentation. Our findings indicate that EDN significantly suppressed the expression of phosphorylated forms of phosphatidylinositol 3-kinase (PI3K)/AKT, phosphorylated p38 kinases (p-p38), phosphorylated extracellular signal-regulated kinase-1 (p-ERK1), phosphorylated c-Jun N-terminal kinase (p-JNK) in GES-1 cells infected with H. pylori. Additionally, EDN notably enhanced the expression of antioxidant proteins nuclear factor erythroid factor-2 (Nrf2) in H. pylori-infected cells. In summary, EDN shows promising potential in preventing H. pylori-associated infections and their associated resistance, making it a viable candidate for the prevention of H. pylori-induced gastric cancer.

Keywords
Emodin; gastric cancer; H. Pylori; GES-1 cell line; Inflammation
Funding
None.
Conflict of interest
There is no competing interest.
References
  1. Rawla P, Barsouk A. Epidemiology of gastric cancer: global trends, risk factors and prevention. Prz Gastroenterol. 2019;14(1):26-38.

 

  1. Kashyap D, Baral B, Jakhmola S, Singh AK, Jha HC. Helicobacter pylori and Epstein-Barr Virus Coinfection Stimulates Aggressiveness in Gastric Cancer through the Regulation of Gankyrin. mSphere. 2021 Oct 27;6(5):e0075121.

 

  1. Kusters JG, van Vliet AH, Kuipers EJ. Pathogenesis of Helicobacter pylori infection. Clin Microbiol Rev. 2006 Jul;19(3):449-90.

 

  1. Reyes VE. Helicobacter pylori and Its Role in Gastric Cancer. Microorganisms. 2023 May 17;11(5):1312.

 

  1. Butcher LD, den Hartog G, Ernst PB, Crowe SE. Oxidative Stress Resulting From Helicobacter pylori Infection Contributes to Gastric Carcinogenesis. Cell Mol Gastroenterol Hepatol. 2017 Feb 20;3(3):316-322.

 

  1. Sah DK, Arjunan A, Lee B, Jung YD. Reactive Oxygen Species and H. pylori Infection: A Comprehensive Review of Their Roles in Gastric Cancer Development. Antioxidants (Basel). 2023 Sep 2;12(9):1712.

 

  1. Han L, Shu X, Wang J. Helicobacter pylori-Mediated Oxidative Stress and Gastric Diseases: A Review. Front Microbiol. 2022 Feb 8;13:811258.

 

  1. Kim J, Cha YN, Surh YJ. A protective role of nuclear factor-erythroid 2-related factor-2 (Nrf2) in inflammatory disorders. Mutat Res. 2010 Aug 7;690(1-2):12-23.

 

  1. Ngo V, Duennwald ML. Nrf2 and Oxidative Stress: A General Overview of Mechanisms and Implications in Human Disease. Antioxidants (Basel). 2022 Nov 27;11(12):2345.

 

  1. Boyanova, L., Hadzhiyski, P., Kandilarov, N., Markovska, R., & Mitov, I. (2019). Multidrug resistance in Helicobacter pylori: current state and future directions. Expert review of clinical pharmacology12(9), 909-915.

 

  1. Ding, S. Z. (2020). Global whole family based-Helicobacter pylori eradication strategy to prevent its related diseases and gastric cancer. World Journal of Gastroenterology26(10), 995.

 

  1. Chiș, A. A., Rus, L. L., Morgovan, C., Arseniu, A. M., Frum, A., Vonica-Țincu, A. L., ... & Dobrea, C. M. (2022). Microbial resistance to antibiotics and effective antibiotherapy. Biomedicines10(5), 1121.

 

  1. Tshibangu-Kabamba, E., & Yamaoka, Y. (2021). Helicobacter pylori infection and antibiotic resistance—from biology to clinical implications. Nature Reviews Gastroenterology & Hepatology18(9), 613-629.

 

  1. Krzyżek, P., Paluch, E., & Gościniak, G. (2020). Synergistic therapies as a promising option for the treatment of antibiotic-resistant Helicobacter pylori. Antibiotics9(10), 658.

 

  1. Monisha, B. A., Kumar, N., & Tiku, A. B. (2016). Emodin and its role in chronic diseases. Anti-inflammatory Nutraceuticals and Chronic Diseases, 47-73.

 

  1. Long H, Chen H, Yan J, Cheng H. Emodin exerts antitumor effects in ovarian cancer cell lines by preventing the development of cancer stem cells via epithelial mesenchymal transition. Oncol Lett. 2022 Mar;23(3):95.

 

  1. Iwanowycz S, Wang J, Hodge J, Wang Y, Yu F, Fan D. Emodin Inhibits Breast Cancer Growth by Blocking the Tumor-Promoting Feedforward Loop between Cancer Cells and Macrophages. Mol Cancer Ther. 2016 Aug;15(8):1931-42.

 

  1. Zhang FY, Li RZ, Xu C, Fan XX, Li JX, Meng WY, Wang XR, Liang TL, Guan XX, Pan HD, Liu L, Yao XJ, Wu QB, Leung EL. Emodin induces apoptosis and suppresses non-small-cell lung cancer growth via downregulation of sPLA2-IIa. Phytomedicine. 2022 Jan;95:153786.

 

  1. Min H, Niu M, Zhang W, Yan J, Li J, Tan X, Li B, Su M, Di B, Yan F. Emodin reverses leukemia multidrug resistance by competitive inhibition and downregulation of P-glycoprotein. PLoS One. 2017 Nov 9;12(11):e0187971

 

  1. Ding X, Zhu J, Wang X, Zhou W, Wu K, Zhou Z, Zhou K, Wu D, Jiao J, Xia Y, Wang X. Different cytotoxicity of disinfection by-product haloacetamides on two exposure pathway-related cell lines: Human gastric epithelial cell line GES-1 and immortalized human keratinocyte cell line HaCaT. Sci Total Environ. 2019 Nov 20;692:1267-1275.

 

  1. Ouyang Y, Li L, Ling P. Nobiletin Inhibits Helicobacterium pylori Infection-Induced Gastric Carcinogenic Signaling by Blocking Inflammation, Apoptosis, and Mitogen-Activated Protein Kinase Events in Gastric Epithelial-1 Cells. J Environ Pathol Toxicol Oncol. 2020;39(1):77-88.

 

  1. Velilla E, López-Béjar M, Rodríguez-González E, Vidal F, Paramio MT. Effect of Hoechst 33342 staining on developmental competence of prepubertal goat oocytes. Zygote. 2002 Aug;10(3):201-8.

 

  1. Balupillai A, Nagarajan RP, Ramasamy K, Govindasamy K, Muthusamy G. Caffeic acid prevents UVB radiation induced photocarcinogenesis through regulation of PTEN signaling in human dermal fibroblasts and mouse skin. Toxicol Appl Pharmacol. 2018 Aug 1;352:87-96.

 

  1. Kusters JG, van Vliet AH, Kuipers EJ. Pathogenesis of Helicobacter pylori infection. Clin Microbiol Rev. 2006 Jul;19(3):449-90.

 

  1. Sah DK, Arjunan A, Lee B, Jung YD. Reactive Oxygen Species and H. pyloriInfection: A Comprehensive Review of Their Roles in Gastric Cancer Development. Antioxidants (Basel). 2023 Sep 2;12(9):1712. 

 

  1. Kopustinskiene DM, Jakstas V, Savickas A, Bernatoniene J. Flavonoids as Anticancer Agents. Nutrients. 2020 Feb 12;12(2):457.

 

  1. Han H, Lim JW, Kim H. Astaxanthin Inhibits Helicobacter pylori-induced Inflammatory and Oncogenic Responses in Gastric Mucosal Tissues of Mice. J Cancer Prev. 2020 Dec 30;25(4):244-251.

 

  1. Xu SJ, Wang X, Wang TY, Lin ZZ, Hu YJ, Huang ZL, Yang XJ, Xu P. Flavonoids from RosaroxburghiiTratt prevent reactive oxygen species-mediated DNA damage in thymus cells both combined with and without PARP-1 expression after exposure to radiation in vivo. Aging (Albany NY). 2020 Aug 29;12(16):16368-16389.

 

  1. Han H, Lim JW, Kim H. Lycopene Inhibits Activation of Epidermal Growth Factor Receptor and Expression of Cyclooxygenase-2 in Gastric Cancer Cells. Nutrients. 2019 Sep 5;11(9):2113. 

 

  1. Kandan PV, Balupillai A, Kanimozhi G, Khan HA, Alhomida AS, Prasad NR. Opuntiol Prevents Photoaging of Mouse Skin viaBlocking Inflammatory Responses and
    Collagen Degradation. Oxid Med Cell Longev. 2020 Nov 30;2020:5275178.

 

  1. Wang L, Zhang X, Xiong X, Zhu H, Chen R, Zhang S, Chen G, Jian Z. Nrf2 Regulates Oxidative Stress and Its Role in Cerebral Ischemic Stroke. Antioxidants (Basel). 2022 Nov 30;11(12):2377.

 

  1. Lin W, Zhong M, Yin H, Chen Y, Cao Q, Wang C, Ling C. Emodin induces hepatocellular carcinoma cell apoptosis through MAPK and PI3K/AKT signaling pathways in vitro and in vivo. Oncol Rep. 2016 Aug;36(2):961-7. 

 

  1. Sabitha R, Nishi K, Gunasekaran VP, Agilan B, David E, Annamalai G, Vinothkumar R, Perumal M, Subbiah L, Ganeshan M. p-Coumaric acid attenuates alcohol exposed hepatic injury through MAPKs, apoptosis and Nrf2 signaling in experimental models. Chem Biol Interact. 2020 Apr 25;321:109044. 

 

  1. Matsuoka T, Yashiro M. The Role of PI3K/Akt/mTOR Signaling in Gastric Carcinoma. Cancers (Basel). 2014 Jul 7;6(3):1441-63.

 

  1. Li F, Wang S, Niu M. Scutellarin Inhibits the Growth and EMT of Gastric Cancer Cells through Regulating PTEN/PI3K Pathway. Biol Pharm Bull. 2021;44(6):780-788.

 

  1. Elmore S. Apoptosis: a review of programmed cell death. Toxicol Pathol. 2007 Jun;35(4):495-516. doi: 10.1080/01926230701320337.

 

  1. Alzahrani S, Lina TT, Gonzalez J, Pinchuk IV, Beswick EJ, Reyes VE. Effect of Helicobacter pylori on gastric epithelial cells. World J Gastroenterol. 2014 Sep 28;20(36):12767-80.
Share
Back to top
Cancer Plus, Electronic ISSN: 2661-3840 Print ISSN: 2661-3832, Published by AccScience Publishing