The effects of ellagic acid and other pomegranate (Punica granatum L.) derivatives on human gastric cancer AGS cells

Author:

Cheshomi Hamid1,Bahrami Ahmad Reza12,Rafatpanah Houshang3,Matin Maryam M14ORCID

Affiliation:

1. Department of Biology, Faculty of Science, Ferdowsi University of Mashhad, Mashhad, Iran

2. Industrial Biotechnology Research Group, Institute of Biotechnology, Ferdowsi University of Mashhad, Mashhad, Iran

3. Immunology Research Center, Inflammation and Inflammatory Diseases Division, Mashhad University of Medical Sciences, Mashhad, Iran

4. Novel Diagnostics and Therapeutics Research Group, Institute of Biotechnology, Ferdowsi University of Mashhad, Mashhad, Iran

Abstract

Although surgery with or without (neo)adjuvant chemo/radiotherapy, as the standard treatments, can be suitable therapeutic strategies for gastric cancer, side effects and drug resistance are two main treatment obstacles. It has been discovered that pomegranate and its natural derivatives, especially ellagic acid (EA), offer significant anti-cancer effects while causing trivial side effects. In this study, we aimed to explore the anti-cancer effects of EA on a human gastric adenocarcinoma cell line (AGS) as well as in immunocompromised mice bearing human gastric tumors, for the first time. HPLC was used for determining EA in samples. MTT assay, apoptosis and scratch assay, gelatin zymography, and quantitative RT-PCR were used to determine the anti-cancer properties of different concentrations of pomegranate fruit juice, pomegranate peel extract, and EA. Furthermore, the effects of these compounds were investigated on immunosuppressed C57BL/6 mice carrying human gastric cancer tumors. EA could inhibit the proliferation and migration of gastric cancer cells. It also had significant effects on reducing both expression and activity of MMP-2 and MMP-9. Further, it was demonstrated that with alterations in the expression of genes involved in apoptosis and inflammation including P53, BAX, APAF1, BCL2, iNOS, NF-κB, IL-8, and TNF-α, EA treatment led to increased cancer cell death and reduced inflammation. Furthermore, its use in mice bearing gastric tumors resulted in a significant reduction in tumor volume without any obvious side effects. Ellagic acid exhibited anti-cancer effects on gastric adenocarcinoma, and can be considered as a safe anti-cancer agent for further preclinical studies on this cancer.

Funder

Ferdowsi University of Mashhad

Publisher

SAGE Publications

Subject

Health, Toxicology and Mutagenesis,Toxicology,General Medicine

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