Ellagic acid and human cancers: a systems pharmacology and docking study to identify principal hub genes and main mechanisms of action

Cheshomi, Hamid; Bahrami, Ahmad Reza; Matin, Maryam Moghaddam

doi:10.1007/s11030-020-10101-6

Cited by 12 publications

(11 citation statements)

References 83 publications

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“… 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. Pomegranate extract enriched in EA can inhibit NF-κB and down-regulate the production of iNOS, COX-2, and TNF-α in colon cancer.…”

Section: Discussionmentioning

confidence: 99%

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

et al. 2023

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Tumor resistance is typically blamed for the failure of radiotherapy and chemotherapy to treat cancer in clinic patients. To improve the cytotoxicity of tumor cells using radiation in conjunction with specific tumor-selective cytotoxic drugs is crucial. Pomegranate has received overwhelmingly positive feedback as a highly nutritious food for enhancing health and treating a variety of ailments. In the present study, we aimed to examine the effects as well as mechanism of action of pomegranate peel extract (PPE) and/or γ-radiation (6-Gy) on hepatocellular carcinoma (HCC) cell lines HepG2. The findings of this study showed that PPE treatment of HepG2 cells considerably slowed the proliferation of cancer cells, and its combination with γ-irradiation potentiated this action. As a key player in tumor proliferation, and inflammatory cascade induction, the down-regulation of STAT3 following treatment of irradiated and non-irradiated HepG2 cells with PPE as recorded in the present work resulted in reduction of tumor growth, via modulating inflammatory response manifested by (down-regulation of TLR4 expression and NFKB level), suppressing survival markers expressed by reduction of JAK, NOTCH1, β-catenin, SOCS3, and enhancing apoptosis (induction of tumor PPAR-γ and caspase-3) followed by changes in redox tone (expressed by increase in Nrf-2, SOD and catalase activities, and decrease in MDA concentration). In conclusion, PPE might possess a considerable therapeutic potential against HCC in addition to its capability to enhance response of HepG2 cells to gamma radiation,

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Section: Discussionmentioning

confidence: 99%

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

et al. 2023

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“…36–38 It has also been approved that EA, as one of the main polyphenols in PFJ and PPE, can have significant anti-tumor effects on different human cancers including bladder, blood, breast, cervical, colorectal, liver, pancreas, and prostate cancer. 10,14,39…”

Section: Discussionmentioning

confidence: 99%

“…11,12 Meanwhile, pomegranate and its related compounds are known as suitable chemopreventive and chemotherapeutic agents in many types of human cancers such as prostate cancer, breast cancer, colorectal cancer, and lung cancer. 13,14…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2022

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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.

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“…Ellagic acid (EA) is a polyphenolic compound that is widely found in plant materials such as pomegranate fruit [ 13 ]. The protective effect of EA against ROS and oxidative stress has been documented in both in vitro and in vivo studies [ 14 ].…”

Section: Introductionmentioning

confidence: 99%

Ellagic Acid Triggers the Necrosis of Differentiated Human Enterocytes Exposed to 3-Nitro-Tyrosine: An MS-Based Proteomic Study

et al. 2022

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To study the molecular basis of the toxicological effect of a dietary nitrosated amino acid, namely, 3-nitrotyrosine (3-NT), differentiated human enterocytes were exposed to dietary concentrations of this species (200 μM) and analyzed for flow cytometry, protein oxidation markers and MS-based proteomics. The possible protective role of a dietary phytochemical, ellagic acid (EA) (200 μM), was also tested. The results revealed that cell viability was significantly affected by exposure to 3-NT, with a concomitant significant increase in necrosis (p < 0.05). 3-NT affected several biological processes, such as histocompatibility complex class II (MHC class II), and pathways related to type 3 metabotropic glutamate receptors binding. Addition of EA to 3-NT-treated cells stimulated the toxicological effects of the latter by reducing the abundance of proteins involved in mitochondrial conformation. These results emphasize the impact of dietary nitrosated amino acids in intestinal cell physiology and warn about the potential negative effects of ellagic acid when combined with noxious metabolites.

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Ellagic acid and human cancers: a systems pharmacology and docking study to identify principal hub genes and main mechanisms of action

Cited by 12 publications

References 83 publications

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

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

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

Ellagic Acid Triggers the Necrosis of Differentiated Human Enterocytes Exposed to 3-Nitro-Tyrosine: An MS-Based Proteomic Study

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