Phycocyanin inhibits Helicobacter pylori-induced hyper-proliferation in AGS cells via activation of the ROS/MAPK signaling pathway

Yakun Bi; Daoyan Wu; Xiaojuan Wu; Fei Wang; Hang Yu; Pan Liu; Guzhen Cui; Zhenghong Chen

doi:10.21037/atm-21-7045

Phycocyanin inhibits Helicobacter pylori-induced hyper-proliferation in AGS cells via activation of the ROS/MAPK signaling pathway

Ann Transl Med. 2022 Feb;10(4):176. doi: 10.21037/atm-21-7045.

Authors

Yakun Bi^{1

2}, Daoyan Wu^{1

3}, Xiaojuan Wu^{1

3}, Fei Wang^{1

3}, Hang Yu^{1

3}, Pan Liu^{1

3}, Guzhen Cui^{1

3}, Zhenghong Chen^{1

3}

Affiliations

¹ Key Laboratory of Microbiology and Parasitology of Education Department of Guizhou, School of Basic Medical Science, Guizhou Medical University, Guiyang, China.
² Department of Clinical Laboratory, The Maternal and Child Health Care Hospital of Guizhou Medical University, Guizhou Medical University, Guiyang, China.
³ Key Laboratory of Endemic and Ethnic Diseases of Ministry of Education/Key Laboratory of Environmental Pollution Monitoring and Disease Control, Ministry of Education, Guizhou Medical University, Guiyang, China.

Abstract

Background: Reactive oxygen species (ROS)-induced oxidative stress (OS) and hyper-proliferation of gastric epithelial cells (GECs) due to Helicobacter pylori (Hp) infection are important mechanisms that lead to gastric carcinoma. Phycocyanin is a marine functional food additive with antioxidant and anti-inflammatory properties.

Methods: The flow cytometry was used to detect the effect of 150 µM phycocyanin intervention on the cell cycle of human gastric adenocarcinoma cell line (AGS) infected with Hp. The transcriptomics of AGS cells intervened by 150 µM phycocyanin for 24 h and infected by Hp were detected. Differential gene expression analysis was performed using a cutoff at the normalized gene expression (log2) of 2 and a P-value of <0.05. Comparisons of the transcriptomes were made between the following groups: (I) AGS cells not infected with Hp and not using phycocyanin action and AGS cells infected with Hp only; (II) AGS cells not infected with Hp and not using phycocyanin action and AGS cells infected with phycocyanin action only; and (III) AGS cells infected with Hp only and phycocyanin treated and infected with Hp cells. c-myc and CyclinD1 was detected by quantitative real-time polymerase chain reaction (qRT-PCR) and immunoblotting. Phosphorylation and non-phosphorylation of c-Jun N-terminal kinase (JNK), extracellular signal-regulated kinase (ERK), and p38 Mitogen-activated protein kinase (p38MAPK) were detected by immunoblotting. Intracellular ROS was detected by immunofluorescence.

Results: Phycocyanin alleviates the Hp infection-induced increased cell viability and expression of cell cycle regulatory proteins c-myc and CyclinD1. Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis revealed that the differentially expressed genes in phycocyanin-treated Hp-infected AGS cells were most significantly enriched in the mitogen-activated protein kinase (MAPK) signaling pathway. Phycocyanin could inhibit the Hp infection-induced phosphorylation of JNK, ERK, and p38MAPK and reduce the level of cellular ROS.

Conclusions: This study suggests that phycocyanin can regulate the ROS/MAPK signaling pathway and reduce c-myc and CyclinD1 expression to inhibit the hyper-proliferation of AGS cells. Phycocyanin may serve as an inhibitor of malignant progression of Hp infection-induced gastric disease.

Keywords: Helicobacter pylori (Hp); mitogen-activated protein kinase (MAPK); phycocyanin; proliferation; reactive oxygen species (ROS).