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

Abstract

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,

Antitumoral properties of the pomegranate peel and blueberry extracts against tongue carcinoma (in vitro study)

“…The cytotoxicity and IC50 results of this study on the HNO-97 with PPE treatment are in accordance with the results of colon carcinoma cell line HCT116 where the IC50 was about 74.84 µg/mg ( Keta et al, 2020 ) with the results of Elbakry et al in which liver cancer cell line HepG2 was 83.9 µg/mg ( Elbakry et al, 2023 ) and also with the POMx powder (capsules loaded pomegranate Juice powder),which was 80.53 µg/mg with Ca9-22 oral carcinoma cell line ( Peng et al, 2021 ). These results disagree with the results of melanoma (HTB140), large cell lung carcinoma (HTB177), and breast cancer (MCF7) ( Keta et al, 2020 ).…”

“…The flowcytometric analysis apoptosis assays significant results performed on HNO-97 with the PPE can be conducted to results of hepatocellular carcinoma HEPG2 cell line, Prostate cancer, and cervical cancer ( Deng et al, 2017 , Fazio et al, 2018 , Chaves et al, 2020 , Elbakry et al, 2023 ). These results can also be correlated to Peng et al who studies the effect of POMx, which showed an increasing apoptotic effect of OC (Ca9-22,HSC-3,and OC-2) ( Peng et al, 2021 ).…”

Apoptotic activity of genipin in human oral squamous cell carcinoma in vitro by regulating STAT3 signaling

“…STAT3 functions as a key modulator of several biological processes, including proliferation and apoptotic cell death, in various types of cancer. [13][14][15][16] In our previous study, we found that STAT3 phosphorylation was significantly higher in human OSCC tumors compared with that in the normal oral mucosa. 17 Therefore, we determined whether genipin can suppress STAT3 phosphorylation in human OSCC.…”

A review of experimental and clinical studies on the therapeutic effects of pomegranate (Punica granatum) on non‐alcoholic fatty liver disease: Focus on oxidative stress and inflammation

“…However, recent research has shown that it contains a wealth of bioactive phytochemicals. These compounds can potentially act as antioxidants, physiological agents, antimicrobial agents, and immune system stimulants (Elbakry et al, 2023 ; Smaoui et al, 2019 ). Extracts from the peel have been traditionally used to treat diseases such as type 2 diabetes and carcinoma (Teniente et al, 2023 ; Zare et al, 2023 ).…”

“…Punica granatum (pomegranate) has attracted the attention of researchers due to its potential for the use in medicine and in the food industry. The beneficial compounds found in pomegranates are not only present in the edible part of the fruit but also in non-edible parts such as leaves, buds, bark, seeds, peel, and blossoms (Elbakry et al, 2023;Xiang et al, 2022). Pomegranate supplementation has been demonstrated in multiple studies to have neuroprotective (George et al, 2022), anti-inflammatory (Sayed et al, 2022), hepatoprotective (Al-Gareeb & Mohammed, 2022;Diab et al, 2022), and antioxidant effects (Lotfi et al, 2022).…”