Ellagic acid as a potent anticancer drug: A comprehensive review on in vitro, in vivo, in silico, and drug delivery studies

Mohammadinejad, Arash; Mohajeri, Taraneh; Aleyaghoob, Ghazaleh; Heidarian, Fatemeh; Oskuee, Reza Kazemi

doi:10.1002/bab.2288

Cited by 23 publications

(13 citation statements)

References 171 publications

(277 reference statements)

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“…The results obtained in EA-treated cells were coherent with those found in the literature, in which the ability of EA to enhance calcium metabolism, apoptosis and necrosis in tumor cells, is reported (revised by Mohammadinejad et al, [ 34 ]). However, enterocytes treated with EA led to an attempt to reverse some of the above-mentioned impaired biological functions ( Supplementary Table S8 ).…”

Section: Discussionsupporting

confidence: 90%

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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Section: Discussionsupporting

confidence: 90%

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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“…39 Specifically, the presence of ellagic acid in substantial quantities in unripe raspberries has been identified as selectively inducing apoptosis in cancer cells while leaving normal cells unaffected. 40 In relation to the inhibitory effects of unripe black raspberry and its key component, ellagic acid, on the abnormally hyper-activated AKT and ERK pathways in cancer cells, as observed in our study and other studies, 32,33 the anticancer effect of unripe black raspberry appears to be selective to cancer cells. Taking these results into consideration, it is anticipated that unripe black raspberry could yield a potent anticancer effect in GC.…”

Section: Discussionsupporting

confidence: 81%

“…Ellagic acid and gallic acid have been well-established as potent anticancer agents against various types of cancers, including GC. 30,31 Ellagic acid induces apoptosis and inhibits tumor growth, angiogenesis, and metastasis in in vitro and in vivo models by affecting various genes and regulators related to cancer progression, including PI3 K/AKT, ERK, JAK2/STAT3, and Bcl-2 family members.. 32,33 Gallic acid also induces chemotherapeutic efficacy by modulating various signaling pathways, including EGFR/ERK, PI3 K/ AKT, NF-kB, and JAK/STAT3. 34,35 Consistently, our results showed that ellagic acid and gallic acid have strong inhibitory effects on the invasiveness of AGS and SNU601 GC cells.…”

Section: Discussionmentioning

confidence: 99%

Enhanced Anticancer Effect of Unripe Rubus occidentalis on Gastric Cancer Cells

Kee

Kwon²,

Lee

2023

Natural Product Communications

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Background Black raspberry ( Rubus occidentalis L.) has various bioactive properties, including antioxidant, anti-inflammatory, and anticancer activities. Recently, it has been proposed that the pharmacological efficacy of black raspberry varies with its maturation stage. In the current study, we explored the relationship between maturation stage and anticancer activity in gastric cancer cell lines. Materials and Methods Black raspberry extracts were prepared from both ripe samples 41 days after the fruit set and unripe samples 22 days after the fruit set. Their anticancer activities were compared by assessing the effects on proliferation, apoptosis, invasiveness, and clonogenicity in gastric cancer cell lines. Results Both the ripe and unripe black raspberry samples were effective in inhibiting cell proliferation, invasion, and clonogenic activity. However, the unripe black raspberry extract showed a stronger effect on these activities compared to ripe black raspberry extract. Additionally, the unripe fruit extract increased apoptotic body formation, caspase-3 activity, Bak expression and decreased Bcl2 expression. Furthermore, the unripe black raspberry sample was found to contain higher contents of ellagic acid and gallic acid, and had a stronger suppressive effect on p-ERK and p-AKT protein levels compared to the ripe black raspberry sample. Conclusion Unripe black raspberry has greater anti-cancer effects than fully ripe black raspberry in gastric cancer cells.

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“…Ellagic acid, a hydroxybenzoic acid compound, was initially discovered in oak galls and possesses multiple properties, including neuroprotection, antidiabetic effects, and anti‐hyperlipidemia effects (Evtyugin et al, 2020; Mohammadinejad et al, 2022). This paper focuses on the advancements in understanding how ellagic acid protects against hepatic diseases, which are summarized in Table 3.…”

Section: Mechanisms Of Polyphenolic Compounds Protect Against Hepatic...mentioning

confidence: 99%

Human diet‐derived polyphenolic compounds and hepatic diseases: From therapeutic mechanisms to clinical utilization

Hu,

Zhang,

Wei

et al. 2023

Phytotherapy Research

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This review focuses on the potential ameliorative effects of polyphenolic compounds derived from human diet on hepatic diseases. It discusses the molecular mechanisms and recent advancements in clinical applications. Edible polyphenols have been found to play a therapeutic role, particularly in liver injury, liver fibrosis, NAFLD/NASH, and HCC. In the regulation of liver injury, polyphenols exhibit anti‐inflammatory and antioxidant effects, primarily targeting the TGF‐β, NF‐κB/TLR4, PI3K/AKT, and Nrf2/HO‐1 signaling pathways. In the regulation of liver fibrosis, polyphenolic compounds effectively reverse the fibrotic process by inhibiting the activation of hepatic stellate cells (HSC). Furthermore, polyphenolic compounds show efficacy against NAFLD/NASH by inhibiting lipid oxidation and accumulation, mediated through the AMPK, SIRT, and PPARγ pathways. Moreover, several polyphenolic compounds exhibit anti‐HCC activity by suppressing tumor cell proliferation and metastasis. This inhibition primarily involves blocking Akt and Wnt signaling, as well as inhibiting the epithelial‐mesenchymal transition (EMT). Additionally, clinical trials and nutritional evidence support the notion that certain polyphenols can improve liver disease and associated metabolic disorders. However, further fundamental research and clinical trials are warranted to validate the efficacy of dietary polyphenols.

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Ellagic acid as a potent anticancer drug: A comprehensive review on in vitro, in vivo, in silico, and drug delivery studies

Cited by 23 publications

References 171 publications

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

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

Enhanced Anticancer Effect of Unripe Rubus occidentalis on Gastric Cancer Cells

Human diet‐derived polyphenolic compounds and hepatic diseases: From therapeutic mechanisms to clinical utilization

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