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

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.

Pomegranate Peel Extract Sensitizes Hepatocellular Carcinoma Cells to Ionizing Radiation, Induces Apoptosis and Inhibits MAPK, JAK/STAT3, β-Catenin/NOTCH, and SOCS3 Signaling

“…It has been demonstrated that this substance, besides triggering apoptosis, can halt angiogenesis, tumor cell invasion, and metastasis in a variety of cancers. 55 Additionally, it is found that EA can enhance the impacts of chemotherapy and radiation. 56 According to Cheshomi et al 57 the key signal transduction networks likely used by EA to assert its anticancer actions in human tumors are the P53, WNT/β-catenin, and apoptosis signaling mechanisms.…”

Anticancer applications of phytochemicals in gastric cancer: Effects and molecular mechanism

“…Quercetin inhibited GC cells invasion and migration via the interruption of uPA/uPAR function ( Li and Chen, 2018 ). Study of Hamid and Lim et al (2019) found that Elagic acid inhibits the invasion and migration of GC cells in vivo and in vitro ( Cheshomi et al, 2022 ). Sulforaphane is a phytochemical found in many cruciferous vegetables.…”

“…Lalitha et al reported that isorhamnetin inhibits cell proliferation through the modulation of PPAR-γ activation in gastric cancer (Ramachandran et al, 2012). Data of Hamid et al showed that Elagic acid inhibits the proliferation of GC cells and leads to the reduction of tumor volume in mice (Cheshomi et al, 2022). Sulforaphane is a natural compound of cruciferous vegetables.…”

“…Although surgery with or without chemotherapy/radiotherapy as a standard treatment can be an appropriate treatment strategy for gastric cancer, side effects and drug resistance are the two major obstacles to therapy. It has been found that phytochemical agents exhibited significant anticancer activity while causing trivial side effects ( Cheshomi et al, 2022 ).…”

Pharmacotherapeutic potential of pomegranate in age-related neurological disorders

“…It also altered the expression and activity of MMP-2, MMP-9 (genes participating in migration), P53, BAX, APAF1, BCL2 (genes known for their role in apoptosis), iNOS, NF-κB, IL-8, and TNF-α (genes participating in inflammation). It was also reported to have a significant impact on gastric cancer without any serious side effects (Cheshomi et al, 2022 ).…”