Experimental Evidence of the Antitumor, Antimetastatic and Antiangiogenic Activity of Ellagic Acid

Ceci, Claudia; Lacal, Pedro Miguel; Tentori, Lucio; Martino, Maria Gabriella de; Miano, Roberto; Graziani, Grazia

doi:10.3390/nu10111756

Cited by 201 publications

(153 citation statements)

References 118 publications

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“…Ellagic acid is a polyphenolic compound reported to have antitumor, antimetastatic, and antiangiogenic properties . Studies have reported the presence of phytochemicals such as ellagic acid in SC and is implicated for its beneficial effect .…”

Section: Discussionmentioning

confidence: 99%

“…Apoptosis is involved in the action of several cancer‐chemotherapeutic agents. The selection of new drugs entity associated with apoptosis that would be expected to be effective against tumors and has been introduced into screening for new anticancer drugs . Apoptotic cells exhibit an early loss of phospholipid asymmetry and externalization of phosphatidylserine (PS) residues on the outer layer of the plasma membrane .…”

Section: Discussionmentioning

confidence: 99%

“…Ellagic acid is a polyphenolic compound reported to have antitumor, antimetastatic, and antiangiogenic properties. 17 implicated for its beneficial effect. 8,9 In previous studies, cytotoxic potential of SC seed extract was reported against several cancer cell lines other than HepG2 cells.…”

Section: Discussionmentioning

confidence: 99%

“…drugs entity associated with apoptosis that would be expected to be effective against tumors and has been introduced into screening for new anticancer drugs. 17,18 Apoptotic cells exhibit an early loss of phospholipid asymmetry and externalization of phosphatidylserine (PS) residues on the outer layer of the plasma membrane. 19 The FITC-conjugated annexin V binds to externalized PS and classically used to identify apoptotic cells.…”

Section: Discussionmentioning

confidence: 99%

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Cytotoxic potentials of S. cumini methanolic seed kernel extract in human hepatoma HepG2 cells

Prakash

Ezhilarasan

2019

Environmental Toxicology

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Syzygium cumini (Myrtaceae) is commonly called as Jamun or Jambolan. It has antidiabetic, anti‐inflammatory, antipyretic, and antioxidant activities. Hepatocellular carcinoma is the most frequent and deadliest cancers worldwide. We investigated the cytotoxic potentials of S. cumini methanolic seed kernel extract against human hepatoma HepG2 cells. HepG2 cells were treated with 10, 20, and 40 μg/mL of seed kernel extract for 24 hours and cytotoxic analysis was performed by MTT assay. S. cumini induced apoptosis related morphological changes in HepG2 cells were analyzed by annexin V and propidium iodide double staining. Nuclear fragmentation and chromatin condensation were analyzed by Hoechst nuclear staining. Mitochondrial membrane potential (MMP) was investigated by 5,5′,6,6′‐tetrachloro‐1,1′,3,3′‐tetraethylbenzimidazolyl‐carbocyanine iodide (JC‐1) staining. Protein expressions of hepatocyte nuclear factor‐1α (HFN‐1α) was performed using western blotting. S. cumini treatments caused a significant and a concentration‐dependent increase in the cytotoxicity of HepG2 cells. S. cumini treatments increased the percentage of cells in an early and late apoptosis stage. This treatment also caused chromatin condensation and nuclear fragmentation. Further, S. cumini treatments decreased MMP and also caused a significant downregulation of HFN‐1α protein expression. The present study demonstrated that S. cumini seed extract induced apoptosis in HepG2 cells through decrease in MMP and downregulation of HFN‐1α.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Cytotoxic potentials of S. cumini methanolic seed kernel extract in human hepatoma HepG2 cells

Prakash

Ezhilarasan

2019

Environmental Toxicology

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“…Thus here we tested EA on the Cryptosporidium infection model, we observed anticryptosporidial activity of this compound at micromolar concentrations (Fig 5A). The EA is a natural compound found in strawberries and other fruits, thus this compound have been used as dietary complement to treat several diseases 21,22 , interesting recently this compound showed its antimicrobial activity in the gastrointestinal pathogen Helicobacter pylori 23 . In order to investigate the mechanism of anticryptosporidial activity we evaluated expression proliferation (separine) and apoptosis markers (metacaspase) in the parasite.…”

Section: Discussionmentioning

confidence: 99%

Gene silencing in Cryptosporidium: A rapid approach to identify novel targets for drug development

Castellanos-González

Martinez-Traverso

et al. 2019

Preprint

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24 25 26 27 2 28Abstract: 29 Background: Cryptosporidiosis is a major cause of diarrheal disease. However, the only drug 30 approved for cryptosporidiosis does not work well in high risk populations. Therefore, novel 31 drugs are urgently needed. Then, the identification of novel is necessary to develop new 32 therapies against this parasite. Recently, we have developed a rapid method to block gene 33 expression in Cryptosporidium by using pre-assembled complexes of Cryptosporidium 34 antisense RNA and human protein with slicer activity (Argonaute 2). We hypothesized that 35 structural proteins, proteases, enzymes nucleotide synthesis and transcription factors are 36 essential for parasite development, thus in this work we knock down expression of 4 selected 37 genes: Actin, Apicomplexan DNA-binding protein (AP2), Rhomboid protein 1 (Rom 1) and 38 nucleoside diphosphate kinase (NDK) and elucidated its role during invasion, proliferation and 39 egress of Cryptosporidium. 40 41 Methods: We used protein transfection reagents (PTR) to introduce pre-assembled complexes 42 of antisense RNA and human Argonaute 2 into Cryptosporidium parvum oocysts, the complexes 43 blocked expression of Actin (Act), Transcription factor AP2 (AP2), nucleoside diphosphate 44 kinase (DKN), and rhomboid protein 1 (Rom1). After gene silencing, we evaluated parasite 45 reduction using In vitro models of excystation, invasion, proliferation and egress. We evaluated 46 the potency of ellagic acid, a nucleoside diphosphate kinase inhibitor for anti-cryptosporidial 47 activity using a model of in vitro infection with human HCT-8 cells. 48 49 Results: Silencing of Act, AP2, NDK and Rom1 reduce significantly invasion, proliferation and 50 egress of Cryptosporidium. We showed that silencing of NDK markedly inhibited 51 Cryptosporidium proliferation. This was confirmed by demonstration that ellagic acid reduced 52 the number of parasites at micro molar concentrations (EC 50 =15-30 µM) without showing any 53 toxic effect on human cells. 54 55 Conclusions: Overall the results confirmed the usefulness RNA silencing can be used to 56 identify novel targets for drug development against Cryptosporidium. We identified ellagic acid 57 (EA), a nucleoside diphosphate kinase inhibitor also blocks Cryptosporidium proliferation. Since 58 EA is a dietary supplement approved for human use, then this compound should be studied as 59 a potential treatment for cryptosporidiosis. 3 60 Author summary 61 The World Health Organization reports diarrhea kills around 760,000 children under five every 62 year. Cryptosporidium infection is a leading cause of diarrhea morbidity and mortality. Current 63 therapies to treat this infection are suboptimal, therefore novel treatments are urgently needed. 64 We used genetic tools to identify novel targets for drug development, thus in this work we 65 evaluated the role of 4 genes during Cryptosporidium infection. We demonstrated that silencing 66 of nucleoside-diphosphate kinase (NDK) drastically reduced invasion, proliferation and e...

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Molecular Effects of Bioactive Compounds from Semi‐Desert Plants and Their Uses as Potential Ingredient in Food Products

Palomo‐Ligas

Nery‐Flores

García-Ortiz

et al. 2022

Molecular Mechanisms of Functional Food

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Experimental Evidence of the Antitumor, Antimetastatic and Antiangiogenic Activity of Ellagic Acid

Cited by 201 publications

References 118 publications

Cytotoxic potentials of S. cumini methanolic seed kernel extract in human hepatoma HepG2 cells

Cytotoxic potentials of S. cumini methanolic seed kernel extract in human hepatoma HepG2 cells

Gene silencing in Cryptosporidium: A rapid approach to identify novel targets for drug development

Molecular Effects of Bioactive Compounds from Semi‐Desert Plants and Their Uses as Potential Ingredient in Food Products

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