Effect of Pomegranate Hull Extract on Liver Neoplastic Changes in Rats: More than an Antioxidant

El-Ashmawy, Nahla E.; Khedr, Eman G.; El-Bahrawy, Hoda A.; El-Fattah, Eslam E. Abd

doi:10.1080/01635581.2016.1192205

Cited by 18 publications

(10 citation statements)

References 34 publications

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“… 46 In addition, ROS can activate various signal transduction pathways within cells, including those controlled by NF-kB, Wnt/β-catenin, PI3K, p53, and MAPK which can augment angiogenesis, promote proliferation and halt apoptosis. 47 …”

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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“…The parenteral or oral exposure to small quantities of NDEA results in liver damage and eventually hepatocarcinogenesis which corresponds to human HCC ( El-Ashmawy et al, 2016 ; El-Ashmawy et al, 2017 ). In the present study, the NDEA group showed enlarged livers with a greater liver index indicating that NDEA increased the proliferation of hepatic cells supported by the increase in the necroinflammation score, the upregulation of Ki-67 mRNA expression, and AFP level.…”

Section: Discussionmentioning

confidence: 99%

AKT-AMPKα-mTOR-dependent HIF-1α Activation is a New Therapeutic Target for Cancer Treatment: A Novel Approach to Repositioning the Antidiabetic Drug Sitagliptin for the Management of Hepatocellular Carcinoma

et al. 2022

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HIF-1α is a key factor promoting the development of hepatocellular carcinoma (HCC). As well, AKT-AMPKα-mTOR signaling is a promising target for cancer therapy. Yet, the AKT-AMPKα-mTOR-dependent activation of HIF-1α has not been studied in livers with HCC. In addition, the mechanisms underlying the potential antineoplastic effects of sitagliptin (STGPT), an antidiabetic agent, have not yet been elucidated. For that purpose, the N-nitrosodiethylamine (NDEA)-induced HCC mouse model was used in the present study using a dose of 100 mg/kg/week, i.p., for 8 weeks. NDEA-induced HCC mice received STGPT 20, 40, or 80 mg/kg starting on day 61 up to day 120. The present study revealed that STGPT inhibited HIF-1α activation via the interference with the AKT-AMPKα-mTOR axis and the interruption of IKKβ, P38α, and ERK1/2 signals as well. Accordingly, STGPT prolonged the survival, restored the histological features and improved liver function. Additionally, STGPT inhibited angiogenesis, as revealed by a significant downregulation in the VEGF and mRNA expression of CD309 with concomitant inhibition of tissue invasion was evident by an increased ratio of TIMP-1/MMP-2. STGPT exhibited apoptotic stimulatory effect as indicated upon calculating the BCL-2/Bax ratio and by the gene expression of p53. The decrease in AFP and liver index calculation, gene expression of Ki-67 confirmed the antiproliferative activity of STGPT. The anti-inflammatory potential was revealed by the decreased TNF-α level and the downregulation of MCP-1 gene expression. Moreover, an antifibrotic potential was supported by lower levels of TGF-β. These effects appear to be GLP1R-independent. The present study provides a potential basis for repurposing STGPT for the inhibition of HCC progression. Since STGPT is unlikely to cause hypoglycemia, it may be promising as monotherapy or adjuvant therapy to treat diabetic or even normoglycemic patients with HCC.

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“…Different studies on pomegranate have revealed its antineoplastic effect [ 20 , 21 , 22 ]. Patients treated with CDDP alone or in combination with other chemotherapeutic drugs may be exposed to serious adverse effects [ 4 , 23 , 24 ].…”

Section: Discussionmentioning

confidence: 99%

Pomegranate Juice Extract Decreases Cisplatin Toxicity on Peripheral Blood Mononuclear Cells

et al. 2020

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Background: Lung cancer is one of the most prevalent cancers worldwide. Chemotherapy regimens, targeted against lung cancer, are considered an effective treatment; albeit with multiple fatal side effects. An alternative strategy, nowadays, is using natural products. Medicinal plants have been used, in combination with chemotherapy, to ameliorate side effects. Aims: This study aims to investigate the antitumor effect of pomegranate juice (Punica granatum) on human lung adenocarcinoma basal epithelial cells (A549), to check the effect, when combined with low dose cisplatin (CDDP), at different doses. We also have evaluated the potential protective effect of pomegranate on normal peripheral blood mononuclear cells (PBMC). Methods: Phytochemical screening of the extract was done using standard classical tests. Total phenolic and sugar contents were determined using the Folin–Ciocalteu and anthrone reagents, respectively. The antioxidant activity of pomegranate was estimated by the 2,2-diphenyl-1-picrylhydrazyl (DPPH) method. The viability of A549 cells and PBMC was evaluated using the neutral red assay. Results: Our results demonstrated that Punica granatum or pomegranate juice (with different concentrations: 150, 300, 600 µg/mL) contained high levels of flavonoids, alkaloids, tanins, lignins, terpenoids, and phenols. The DPPH method showed that pomegranate juice had a strong antioxidant scavenging activity. Neutral red showed that combining pomegranate juice with low dose CDDP (8 µg/mL) decreased the cell viability of A549 cells, by 64%, compared to treatment with CDDP or pomegranate alone. When added to low dose CDDP, pomegranate increased the viability of normal PBMC cells by 46%. Conclusions: These results demonstrated that pomegranate could potentiate the anticancer effect of low dose CDDP on human lung adenocarcinoma cells (A549 cells) and could as well decrease its toxicity on PBMC.

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Effect of Pomegranate Hull Extract on Liver Neoplastic Changes in Rats: More than an Antioxidant

Cited by 18 publications

References 34 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

AKT-AMPKα-mTOR-dependent HIF-1α Activation is a New Therapeutic Target for Cancer Treatment: A Novel Approach to Repositioning the Antidiabetic Drug Sitagliptin for the Management of Hepatocellular Carcinoma

Pomegranate Juice Extract Decreases Cisplatin Toxicity on Peripheral Blood Mononuclear Cells

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