Skip to main content
Top
Published in: Cancer Cell International 1/2022

Open Access 01-12-2022 | Hepatocellular Carcinoma | Research

Pomegranate juice and punicalagin-mediated chemoprevention of hepatocellular carcinogenesis via regulating miR-21 and NF-κB-p65 in a rat model

Authors: Aya M. Hussein, Nadia M. El-Beih, Menha Swellam, Enas A. El-Hussieny

Published in: Cancer Cell International | Issue 1/2022

Login to get access

Abstract

Background

Hepatocellular carcinoma (HCC) is the most common neoplasm among primary liver malignancies, accounting for 70%–85% of total liver cancer cases worldwide. It is also the second-leading cause of cancer-related death worldwide. Recent research has investigated naturally occurring products high in polyphenolic compounds in the regression and prevention of HCC. This study investigated the chemoprevention effects of pomegranate juice (PJ) and punicalagin (PCG) against diethylnitrosamine (DENA)-induced hepatocarcinogenesis in male albino rats.

Methods

Animals were randomized into six groups and treated for 11 weeks as follows: group 1 was a negative control group, group 2 was treated orally with 10 mL PJ per kilogram body weight (kg bw), group 3 was treated orally with 18.5 mg PCG/kg bw, and groups 4–6 were injected with an intraperitoneal dose of DENA (50 mg/kg bw) weekly beginning in the third week. Group 4 was a HCC control (DENA-treated group), group 5 was HCC + PJ, and group 6 was HCC + PCG.

Results

PJ antagonized DENA-induced elevations of ALAT, TNF-α, NF-κB-p65, GST, MDA, and NO and restored total protein, IL-10, SOD, and CAT levels. Moreover, PJ resulted in downregulation of miR-21, Bcl-2, and Bcl-XL and an upregulation of caspase-3 and Bax mRNA expressions. These chemoprevention effects of PJ also alleviated the hepatic preneoplastic lesions induced by DENA. Although PCG treatment induced some modulation in DENA-treated rats, it did not show potent chemoprevention activity and induced some side effects.

Conclusion

Both of PJ and PCG downregulated miR-21 expression and triggered apoptosis. However, PJ was more effective than pure PCG in alleviating the hepatic antioxidant defense state and the inflammatory status. So, PJ was superior in prevention of DENA-induced hepatocellular carcinogenesis in rats than pure PCG.

Graphical Abstract

Literature
1.
go back to reference Xu X, Lei Y, Chen L, Zhou H, Liu H, Jiang J, et al. Phosphorylation of NF-κBp65 drives inflammation-mediated hepatocellular carcinogenesis and is a novel therapeutic target. J Exp Clin Cancer Res. 2021;40(253):1–17. Xu X, Lei Y, Chen L, Zhou H, Liu H, Jiang J, et al. Phosphorylation of NF-κBp65 drives inflammation-mediated hepatocellular carcinogenesis and is a novel therapeutic target. J Exp Clin Cancer Res. 2021;40(253):1–17.
2.
go back to reference Kurma K, Manches O, Chuffart F, Sturm N, Gharzeddine K, Zhang J, et al. DEN-induced rat model reproduces key features of human hepatocellular carcinoma. Cancers. 2021;13:4981.PubMedPubMedCentralCrossRef Kurma K, Manches O, Chuffart F, Sturm N, Gharzeddine K, Zhang J, et al. DEN-induced rat model reproduces key features of human hepatocellular carcinoma. Cancers. 2021;13:4981.PubMedPubMedCentralCrossRef
3.
go back to reference Nasr MA, Salah RA, Abd Elkodous M, Elshenawy SE, El-Badri N. Dysregulated microRNA fingerprints and methylation patterns in hepatocellular carcinoma, cancer stem cells, and mesenchymal stem cells. Front Cell Dev Biol. 2019;7:1–18.CrossRef Nasr MA, Salah RA, Abd Elkodous M, Elshenawy SE, El-Badri N. Dysregulated microRNA fingerprints and methylation patterns in hepatocellular carcinoma, cancer stem cells, and mesenchymal stem cells. Front Cell Dev Biol. 2019;7:1–18.CrossRef
4.
go back to reference Bartolini D, Dallaglio K, Torquato P, Piroddi M, Galli F. Nrf2-p62 autophagy pathway and its response to oxidative stress in hepatocellular carcinoma. Transl Res. 2018;193:54–71.PubMedCrossRef Bartolini D, Dallaglio K, Torquato P, Piroddi M, Galli F. Nrf2-p62 autophagy pathway and its response to oxidative stress in hepatocellular carcinoma. Transl Res. 2018;193:54–71.PubMedCrossRef
5.
go back to reference Locatelli C, Jardim JKB, Zancanaro V. Role of antioxidants in the treatment of hepatocellular carcinoma: Integrative review. Res Soc Dev. 2021;10(1):1–20.CrossRef Locatelli C, Jardim JKB, Zancanaro V. Role of antioxidants in the treatment of hepatocellular carcinoma: Integrative review. Res Soc Dev. 2021;10(1):1–20.CrossRef
7.
go back to reference Weis A, Marquart L, Calvopina DA, Genz B, Ramm GA, Skoien R. Serum microRNAs as biomarkers in hepatitis C: preliminary evidence of a microRNA panel for the diagnosis of hepatocellular carcinoma. Int J Mol Sci. 2019;20(4):864.PubMedCentralCrossRef Weis A, Marquart L, Calvopina DA, Genz B, Ramm GA, Skoien R. Serum microRNAs as biomarkers in hepatitis C: preliminary evidence of a microRNA panel for the diagnosis of hepatocellular carcinoma. Int J Mol Sci. 2019;20(4):864.PubMedCentralCrossRef
8.
go back to reference Chauhan R, Lahiri N. Tissue- and serum-associated biomarkers of hepatocellular carcinoma. Biomark Cancer. 2016;8(1):37–55.PubMedPubMedCentral Chauhan R, Lahiri N. Tissue- and serum-associated biomarkers of hepatocellular carcinoma. Biomark Cancer. 2016;8(1):37–55.PubMedPubMedCentral
9.
go back to reference Schetter AJ, Leung SY, Sohn JJ. MicroRNA expression profiles associated with prognosis and therapeutic outcome in colon adenocarcinoma. JAMA. 2008;299:425–36.PubMedPubMedCentralCrossRef Schetter AJ, Leung SY, Sohn JJ. MicroRNA expression profiles associated with prognosis and therapeutic outcome in colon adenocarcinoma. JAMA. 2008;299:425–36.PubMedPubMedCentralCrossRef
10.
go back to reference Zhang J, Jiao J, Cermelli S, Muir K, Jung KH, Zou R, Rashid A, Gagea M, Zabludoff S, Kalluri R, Beretta L. Mir-21 inhibition reduces liver fibrosis and prevents tumor development by inducing apoptosis of CD24+ progenitor cells. Cancer Res. 2015;75(9):1859–67.PubMedPubMedCentralCrossRef Zhang J, Jiao J, Cermelli S, Muir K, Jung KH, Zou R, Rashid A, Gagea M, Zabludoff S, Kalluri R, Beretta L. Mir-21 inhibition reduces liver fibrosis and prevents tumor development by inducing apoptosis of CD24+ progenitor cells. Cancer Res. 2015;75(9):1859–67.PubMedPubMedCentralCrossRef
11.
go back to reference Santarpia L, Lippman SL, El-Naggar AK. Targeting the mitogen-activated protein kinase ras-raf signaling pathway in cancer therapy. Expert Opin Ther Targets. 2012;16(1):103–19.PubMedPubMedCentralCrossRef Santarpia L, Lippman SL, El-Naggar AK. Targeting the mitogen-activated protein kinase ras-raf signaling pathway in cancer therapy. Expert Opin Ther Targets. 2012;16(1):103–19.PubMedPubMedCentralCrossRef
12.
go back to reference Cragg GM, Pezzuto JM. Natural products as a vital source for the discovery of cancer chemotherapeutic and chemopreventive agents: review. Med Princ Pract. 2016;25(2):41–59.PubMedCrossRef Cragg GM, Pezzuto JM. Natural products as a vital source for the discovery of cancer chemotherapeutic and chemopreventive agents: review. Med Princ Pract. 2016;25(2):41–59.PubMedCrossRef
13.
go back to reference Costantini S, Rusolo F, Vito V, Moccia S, Picariello G, Capone F, et al. Potential anti-inflammatory effects of the hydrophilic fraction of pomegranate (Punica granatum L.) seed oil on breast cancer cell lines. Molecules. 2014;19:8644–60.PubMedPubMedCentralCrossRef Costantini S, Rusolo F, Vito V, Moccia S, Picariello G, Capone F, et al. Potential anti-inflammatory effects of the hydrophilic fraction of pomegranate (Punica granatum L.) seed oil on breast cancer cell lines. Molecules. 2014;19:8644–60.PubMedPubMedCentralCrossRef
14.
go back to reference Panth N, Manandhar B, Paude KR. Anticancer activity of Punica granatum (Pomegranate): review. Phytother Res. 2017;31:568–78.PubMedCrossRef Panth N, Manandhar B, Paude KR. Anticancer activity of Punica granatum (Pomegranate): review. Phytother Res. 2017;31:568–78.PubMedCrossRef
15.
go back to reference Bishayee A, Mandal A, Bhattacharyya P, Bhatia D. Pomegranate exerts chemoprevention of experimentally induced mammary tumorigenesis by suppression of cell proliferation and induction of apoptosis. Nutr Cancer. 2016;68(1):120–30.PubMedCrossRef Bishayee A, Mandal A, Bhattacharyya P, Bhatia D. Pomegranate exerts chemoprevention of experimentally induced mammary tumorigenesis by suppression of cell proliferation and induction of apoptosis. Nutr Cancer. 2016;68(1):120–30.PubMedCrossRef
16.
go back to reference Rapa SF, Magliocca G, Pepe G, Amodio G, Autore G, Campiglia P, et al. Protective effect of pomegranate on oxidative stress and inflammatory response induced by 5-fluorouracil in human keratinocytes. Antioxidants. 2021;10:203.PubMedPubMedCentralCrossRef Rapa SF, Magliocca G, Pepe G, Amodio G, Autore G, Campiglia P, et al. Protective effect of pomegranate on oxidative stress and inflammatory response induced by 5-fluorouracil in human keratinocytes. Antioxidants. 2021;10:203.PubMedPubMedCentralCrossRef
17.
go back to reference Tang Q, Wang Q, Zhang Q, Lin S, Zhu Y, Yang X, et al. Gene expression, regulation of DEN and HBx induced HCC mice models and comparisons of tumor, para-tumor and normal tissues. BMC Cancer. 2017;17:862.PubMedPubMedCentralCrossRef Tang Q, Wang Q, Zhang Q, Lin S, Zhu Y, Yang X, et al. Gene expression, regulation of DEN and HBx induced HCC mice models and comparisons of tumor, para-tumor and normal tissues. BMC Cancer. 2017;17:862.PubMedPubMedCentralCrossRef
18.
go back to reference Cheng Y, Luo RC, Zheng H, Wang B, Liu YH, Liu DL, et al. Synergistic anti-tumor efficacy of sorafenib and fluvastatin in hepatocellular carcinoma. Oncotarget. 2017;8(14):23265–76.PubMedPubMedCentralCrossRef Cheng Y, Luo RC, Zheng H, Wang B, Liu YH, Liu DL, et al. Synergistic anti-tumor efficacy of sorafenib and fluvastatin in hepatocellular carcinoma. Oncotarget. 2017;8(14):23265–76.PubMedPubMedCentralCrossRef
19.
go back to reference Ahmed OM, Ashour MB, Fahim HI, AbouZid SF, Ahmed RG, Gaid MA. Punica granatum mitigates 7, 12-dimethylbenz[a]anthracene and ccl4induced oxidative stress and hepatic precancerous lesions in wistar rats. Indo Am J Pharm Res. 2016;6(9):6493–509. Ahmed OM, Ashour MB, Fahim HI, AbouZid SF, Ahmed RG, Gaid MA. Punica granatum mitigates 7, 12-dimethylbenz[a]anthracene and ccl4induced oxidative stress and hepatic precancerous lesions in wistar rats. Indo Am J Pharm Res. 2016;6(9):6493–509.
20.
go back to reference Ahmed OM, Ashour MB, Fahim HI, AbouZid SF, Ahmed RG, Gaid MA. Ameliorative effects of Punica granatum juice and extracts against 7,12-dimethylbenz (a) anthracene and carbon tetrachloride-induced cardiorenal toxicity in albino rats. SM J Biol. 2016;2(2):1011. Ahmed OM, Ashour MB, Fahim HI, AbouZid SF, Ahmed RG, Gaid MA. Ameliorative effects of Punica granatum juice and extracts against 7,12-dimethylbenz (a) anthracene and carbon tetrachloride-induced cardiorenal toxicity in albino rats. SM J Biol. 2016;2(2):1011.
21.
go back to reference El-Beih NM, Ramadan G, El-Husseiny EA, Hussein AM. Effects of pomegranate aril juice and its punicalagin on some key regulators of insulin resistance and oxidative liver injury in streptozotocin-nicotinamide type 2 diabetic rats. Mol Biol Rep. 2019;46(4):3701–11.PubMedCrossRef El-Beih NM, Ramadan G, El-Husseiny EA, Hussein AM. Effects of pomegranate aril juice and its punicalagin on some key regulators of insulin resistance and oxidative liver injury in streptozotocin-nicotinamide type 2 diabetic rats. Mol Biol Rep. 2019;46(4):3701–11.PubMedCrossRef
22.
go back to reference Yoshioka T, Kawada K, Shimada T, Mori M. Lipid peroxidation in maternal and cord blood and protective mechanism against activated-oxygen toxicity in the blood. Am J Obstet Gynecol. 1979;135:372–6.PubMedCrossRef Yoshioka T, Kawada K, Shimada T, Mori M. Lipid peroxidation in maternal and cord blood and protective mechanism against activated-oxygen toxicity in the blood. Am J Obstet Gynecol. 1979;135:372–6.PubMedCrossRef
23.
go back to reference Montgomery HAC, Dymock JE. The determination of nitrite in water. Analyst. 1961;86:414–6. Montgomery HAC, Dymock JE. The determination of nitrite in water. Analyst. 1961;86:414–6.
25.
go back to reference Nishikimi M, Rao NA, Yagi K. The occurrence of superoxide anion in the reaction of reduced phenazine methosulphate and molecular oxygen. Biochem Bioph Res Commun. 1972;46(2):849–54.CrossRef Nishikimi M, Rao NA, Yagi K. The occurrence of superoxide anion in the reaction of reduced phenazine methosulphate and molecular oxygen. Biochem Bioph Res Commun. 1972;46(2):849–54.CrossRef
26.
go back to reference Habig WH, Pabst MJ, Jakoby WB. Glutathione S-transferases: the first enzymatic step in mercapturic acid formation. J boil Chem. 1974;249:7130–9.CrossRef Habig WH, Pabst MJ, Jakoby WB. Glutathione S-transferases: the first enzymatic step in mercapturic acid formation. J boil Chem. 1974;249:7130–9.CrossRef
27.
go back to reference Livak K, Schmittgen D. Analysis of relative gene expression data using real-time quantitative PCR and the 2^(−ΔΔCT) method. Methods. 2001;25:402–8.PubMedCrossRef Livak K, Schmittgen D. Analysis of relative gene expression data using real-time quantitative PCR and the 2^(−ΔΔCT) method. Methods. 2001;25:402–8.PubMedCrossRef
28.
go back to reference Ibrahim NE, Aboulthana WM, Sahu RK. Hepatocellular carcinoma: causes and prevention. UK J Pharm Biosci. 2018;6(5):48–55.CrossRef Ibrahim NE, Aboulthana WM, Sahu RK. Hepatocellular carcinoma: causes and prevention. UK J Pharm Biosci. 2018;6(5):48–55.CrossRef
29.
go back to reference Pacheco-Palencia LA, Noratto G, Hingorani L, Talcott ST, Mertens-Talcott SU. Protective effects of standardized pomegranate (Punica granatum L.) polyphenolic extract in ultraviolet-irradiated human skin fibroblasts. J Agr Food Chem. 2008;56(18):8434–41.CrossRef Pacheco-Palencia LA, Noratto G, Hingorani L, Talcott ST, Mertens-Talcott SU. Protective effects of standardized pomegranate (Punica granatum L.) polyphenolic extract in ultraviolet-irradiated human skin fibroblasts. J Agr Food Chem. 2008;56(18):8434–41.CrossRef
30.
go back to reference Seeram NP, Adams LS, Henning SM, Niu Y, Zhang Y, Nair MG, et al. In vitro antiproliferative, apoptotic and antioxidant activities of punicalagin, ellagic acid and a total pomegranate tannin extract are enhanced in combination with other polyphenols as found in pomegranate juice. J Nutr Biochem. 2005;16(6):360–7.PubMedCrossRef Seeram NP, Adams LS, Henning SM, Niu Y, Zhang Y, Nair MG, et al. In vitro antiproliferative, apoptotic and antioxidant activities of punicalagin, ellagic acid and a total pomegranate tannin extract are enhanced in combination with other polyphenols as found in pomegranate juice. J Nutr Biochem. 2005;16(6):360–7.PubMedCrossRef
31.
go back to reference Syed DN, Chamcheu JC, Adhami VM, Mukhtar H. Pomegranate extracts and cancer prevention: molecular and cellular activities. Anticancer Agents Med Chem. 2013;13(8):1149–61.PubMedPubMedCentralCrossRef Syed DN, Chamcheu JC, Adhami VM, Mukhtar H. Pomegranate extracts and cancer prevention: molecular and cellular activities. Anticancer Agents Med Chem. 2013;13(8):1149–61.PubMedPubMedCentralCrossRef
32.
go back to reference Bishayee A, Bhatia D, Thoppil RJ, Darvesh AS, Nevo E, Lansky EB. Pomegranate-mediated chemoprevention of experimental hepatocarcinogenesis involves Nrf2-regulated antioxidant mechanisms. Carcinogenesis. 2011;32(6):888–96.PubMedPubMedCentralCrossRef Bishayee A, Bhatia D, Thoppil RJ, Darvesh AS, Nevo E, Lansky EB. Pomegranate-mediated chemoprevention of experimental hepatocarcinogenesis involves Nrf2-regulated antioxidant mechanisms. Carcinogenesis. 2011;32(6):888–96.PubMedPubMedCentralCrossRef
34.
go back to reference Farber E, Sarma DS. Hepatocarcinogenesis: a dynamic cellular perspective: review. Lab Invest. 1987;56(1):4–22.PubMed Farber E, Sarma DS. Hepatocarcinogenesis: a dynamic cellular perspective: review. Lab Invest. 1987;56(1):4–22.PubMed
35.
go back to reference Bassiri-Jahromi S. Punica granatum (Pomegranate) activity in health promotion and cancer prevention. Oncol Rev. 2018;12(1):345.PubMedPubMedCentral Bassiri-Jahromi S. Punica granatum (Pomegranate) activity in health promotion and cancer prevention. Oncol Rev. 2018;12(1):345.PubMedPubMedCentral
36.
go back to reference Kumar RS, Kumar SV, Rajkapoor B, Pravin N, Mahendiran D. Chemopreventive effect of Indigofera linnaei extract against diethylnitrosamine induced hepatocarcinogenesis in rats. J Appl Pharm Sci. 2016;6(11):199–209.CrossRef Kumar RS, Kumar SV, Rajkapoor B, Pravin N, Mahendiran D. Chemopreventive effect of Indigofera linnaei extract against diethylnitrosamine induced hepatocarcinogenesis in rats. J Appl Pharm Sci. 2016;6(11):199–209.CrossRef
37.
go back to reference Assar DH, Mokhbatly AA, Ghazy EW, Ragab AE, Abou Asa S, Abdo W, et al. Ameliorative effects of Aspergillus awamori against the initiation of hepatocarcinogenesis induced by diethylnitrosamine in a rat model: regulation of cyp19 and p53 gene expression. Antioxidants. 2021;10(922):1–16. Assar DH, Mokhbatly AA, Ghazy EW, Ragab AE, Abou Asa S, Abdo W, et al. Ameliorative effects of Aspergillus awamori against the initiation of hepatocarcinogenesis induced by diethylnitrosamine in a rat model: regulation of cyp19 and p53 gene expression. Antioxidants. 2021;10(922):1–16.
38.
go back to reference Sadik NAH, El-Maraghy SA, Ismail MF. Diethylnitrosamine-induced hepatocarcinogenesis in rats: possible chemoprevention by blueberries. Afr J Biochem Res. 2008;2:81–7. Sadik NAH, El-Maraghy SA, Ismail MF. Diethylnitrosamine-induced hepatocarcinogenesis in rats: possible chemoprevention by blueberries. Afr J Biochem Res. 2008;2:81–7.
39.
go back to reference Jayakumar S, Madankumar A, Asokkumar S, Raghunandhakumar S, Gokula Dhas K, Kamaraj S, et al. Potential preventive effect of carvacrol against diethylnitrosamine-induced hepatocellular carcinoma in rats. Mol Cell Biochem. 2012;360:51–60.PubMedCrossRef Jayakumar S, Madankumar A, Asokkumar S, Raghunandhakumar S, Gokula Dhas K, Kamaraj S, et al. Potential preventive effect of carvacrol against diethylnitrosamine-induced hepatocellular carcinoma in rats. Mol Cell Biochem. 2012;360:51–60.PubMedCrossRef
40.
go back to reference Mokh AA, Abdelhady DH, Ghazy EW, Aboumosalem H, Goda WM. Sesame oil mitigates initiation stage of diethynitrosamine hepatocarcinogenesis in rats. Slov Vet Res. 2019;56(22):487–98. Mokh AA, Abdelhady DH, Ghazy EW, Aboumosalem H, Goda WM. Sesame oil mitigates initiation stage of diethynitrosamine hepatocarcinogenesis in rats. Slov Vet Res. 2019;56(22):487–98.
41.
go back to reference Husain H, Latief U, Ahmad R. Pomegranate action in curbing the incidence of liver injury triggered by diethylnitrosamine by declining oxidative stress via Nrf2 and NFκB regulation. Sci Rep. 2018;8(1):1–17.CrossRef Husain H, Latief U, Ahmad R. Pomegranate action in curbing the incidence of liver injury triggered by diethylnitrosamine by declining oxidative stress via Nrf2 and NFκB regulation. Sci Rep. 2018;8(1):1–17.CrossRef
42.
go back to reference Lin CC, Hsu YF, Lin TC, Hsu HY. Antioxidant and hepatoprotective effects of punicalagin and punicalin on acetaminopheninduced liver damage in rats. Phytother Res. 2001;15(3):206–12.PubMedCrossRef Lin CC, Hsu YF, Lin TC, Hsu HY. Antioxidant and hepatoprotective effects of punicalagin and punicalin on acetaminopheninduced liver damage in rats. Phytother Res. 2001;15(3):206–12.PubMedCrossRef
43.
go back to reference Rezq AA, Elgazar AF. Hepatoprotective effects of pomegranate and apple juices against N-nitrosodiethylamine - induced hepatocellular carcinoma in male rats. J Stud Search Specifi Edu. 2016;2(1):235–51. Rezq AA, Elgazar AF. Hepatoprotective effects of pomegranate and apple juices against N-nitrosodiethylamine - induced hepatocellular carcinoma in male rats. J Stud Search Specifi Edu. 2016;2(1):235–51.
44.
go back to reference Verna L, Whysner J, Williams GM. N-nitrosodiethylamine mechanistic data and risk assessment: bioactivation, DNA-adduct formation, mutagenicity, and tumor initiation. Pharmacol Ther. 1996;71:57–81.PubMedCrossRef Verna L, Whysner J, Williams GM. N-nitrosodiethylamine mechanistic data and risk assessment: bioactivation, DNA-adduct formation, mutagenicity, and tumor initiation. Pharmacol Ther. 1996;71:57–81.PubMedCrossRef
45.
go back to reference Louie SM, Grossman EA, Crawford LA, Ding L, Camarda R, Huffman TR, et al. GSTP1 is a driver of triple-negative breast cancer cell metabolism and pathogenicity. Cell Chem Biol. 2016;23:567–78.PubMedPubMedCentralCrossRef Louie SM, Grossman EA, Crawford LA, Ding L, Camarda R, Huffman TR, et al. GSTP1 is a driver of triple-negative breast cancer cell metabolism and pathogenicity. Cell Chem Biol. 2016;23:567–78.PubMedPubMedCentralCrossRef
46.
go back to reference Singh RR, Reindl KM. Glutathione S-transferases in cancer: review. Antioxidants. 2021;10(701):1–25. Singh RR, Reindl KM. Glutathione S-transferases in cancer: review. Antioxidants. 2021;10(701):1–25.
47.
go back to reference Hassanen E, Tohamy AF, Issa MY, Ibrahim MA, Farroh KY, Hassan AM. Pomegranate juice diminishes the mitochondria-dependent cell death and nf-kb signaling pathway induced by copper oxide nanoparticles on liver and kidneys of rats. Int J Nanomed. 2019;14:8905–22.CrossRef Hassanen E, Tohamy AF, Issa MY, Ibrahim MA, Farroh KY, Hassan AM. Pomegranate juice diminishes the mitochondria-dependent cell death and nf-kb signaling pathway induced by copper oxide nanoparticles on liver and kidneys of rats. Int J Nanomed. 2019;14:8905–22.CrossRef
48.
go back to reference Aloqbi A, Omar U, Yousr M, Grace M, Lila MA, Howell N. Antioxidant activity of pomegranate juice and punicalagin. Natur Sci. 2016;8:235–46. Aloqbi A, Omar U, Yousr M, Grace M, Lila MA, Howell N. Antioxidant activity of pomegranate juice and punicalagin. Natur Sci. 2016;8:235–46.
49.
go back to reference Ding Y, Wu Z, Wei Y, Shu L, Peng Y. Hepatic inflammation-fibrosis-cancer axis in the rat hepatocellular carcinoma induced by diethylnitrosamine. J Cancer Res Clin Oncol. 2017;143(5):821–34.PubMedCrossRef Ding Y, Wu Z, Wei Y, Shu L, Peng Y. Hepatic inflammation-fibrosis-cancer axis in the rat hepatocellular carcinoma induced by diethylnitrosamine. J Cancer Res Clin Oncol. 2017;143(5):821–34.PubMedCrossRef
51.
go back to reference Tang D, Tao D, Fang Y, Deng C, Xu Q, Zhou J. TNF-alpha promotes invasion and metastasis via NF-kappa B pathway in oral squamous cell carcinoma. Med Sci Monit Basic Res. 2017;23:141–9.PubMedPubMedCentralCrossRef Tang D, Tao D, Fang Y, Deng C, Xu Q, Zhou J. TNF-alpha promotes invasion and metastasis via NF-kappa B pathway in oral squamous cell carcinoma. Med Sci Monit Basic Res. 2017;23:141–9.PubMedPubMedCentralCrossRef
52.
go back to reference Driessler F, Venstrom K, Sabat R, Asadullah K, Schottelius AJ. Molecular mechanisms of interleukin-10-mediated inhibition of NF-κB activity: a role for p50. Clin Exp Immunol. 2004;135(1):64–73.PubMedPubMedCentralCrossRef Driessler F, Venstrom K, Sabat R, Asadullah K, Schottelius AJ. Molecular mechanisms of interleukin-10-mediated inhibition of NF-κB activity: a role for p50. Clin Exp Immunol. 2004;135(1):64–73.PubMedPubMedCentralCrossRef
53.
go back to reference Saleh A, Saed AM, Mansour M. Association of IL-10 and TNF-α polymorphisms with risk and aggressiveness of hepatocellular carcinoma in patients with HCV-related cirrhosis. Egyptian Liver J. 2020;10(43):1–8. Saleh A, Saed AM, Mansour M. Association of IL-10 and TNF-α polymorphisms with risk and aggressiveness of hepatocellular carcinoma in patients with HCV-related cirrhosis. Egyptian Liver J. 2020;10(43):1–8.
54.
go back to reference Haseeb A, Khan NM, Ashruf OS, Haqqi TM. A polyphenol-rich pomegranate fruit extract suppresses NF-κB and IL-6 expression by blocking the activation of IKKβ and NIK in primary human chondrocytes. Phytother Res. 2017;31(5):778–82.PubMedPubMedCentralCrossRef Haseeb A, Khan NM, Ashruf OS, Haqqi TM. A polyphenol-rich pomegranate fruit extract suppresses NF-κB and IL-6 expression by blocking the activation of IKKβ and NIK in primary human chondrocytes. Phytother Res. 2017;31(5):778–82.PubMedPubMedCentralCrossRef
55.
go back to reference Suliman A, Lam A, Datta R, Srivastava RK. Intracellular mechanisms of TRAIL: apoptosis through mitochondrial-dependent and independent pathways. Oncogene. 2001;20(17):2122.PubMedCrossRef Suliman A, Lam A, Datta R, Srivastava RK. Intracellular mechanisms of TRAIL: apoptosis through mitochondrial-dependent and independent pathways. Oncogene. 2001;20(17):2122.PubMedCrossRef
56.
go back to reference Tessitore L. Apoptosis and cell proliferation are involved in the initiation of liver carcinogenesis by a subnecrogenic dose of diethylnitrosamine in refed rats. J Nutr. 2000;130(1):104–10.PubMedCrossRef Tessitore L. Apoptosis and cell proliferation are involved in the initiation of liver carcinogenesis by a subnecrogenic dose of diethylnitrosamine in refed rats. J Nutr. 2000;130(1):104–10.PubMedCrossRef
57.
go back to reference Shaban NZ, El-Kersh MAR, Bader-Eldin MM, Kato SA, Hamoda AF. Effect of Punica granatum (pomegranate) juice extract on healthy liver and hepatotoxicity induced by diethylnitrosamine and phenobarbital in male rats. J Med Food. 2014;17(3):339–49.PubMedCrossRef Shaban NZ, El-Kersh MAR, Bader-Eldin MM, Kato SA, Hamoda AF. Effect of Punica granatum (pomegranate) juice extract on healthy liver and hepatotoxicity induced by diethylnitrosamine and phenobarbital in male rats. J Med Food. 2014;17(3):339–49.PubMedCrossRef
59.
go back to reference Orrenius S, Nicotera P, Zhivotovsky B. Cell death mechanisms and their implications in toxicology. Toxicol Sci. 2011;119(1):3–19.PubMedCrossRef Orrenius S, Nicotera P, Zhivotovsky B. Cell death mechanisms and their implications in toxicology. Toxicol Sci. 2011;119(1):3–19.PubMedCrossRef
60.
go back to reference Redza-Dutordoir M, Averill-Bates DA. Activation of apoptosis signalling pathways by reactive oxygen species: review. Biochim Biophys Acta. 2016;1863(12):2977–92.PubMedCrossRef Redza-Dutordoir M, Averill-Bates DA. Activation of apoptosis signalling pathways by reactive oxygen species: review. Biochim Biophys Acta. 2016;1863(12):2977–92.PubMedCrossRef
61.
go back to reference Chavda V, Chaurasia B, Garg K, Deora H, Umana GE, Palmisciano P, et al. Molecular mechanisms of oxidative stress in stroke and cancer: review. Brain Disorders. 2022;5: 100029.CrossRef Chavda V, Chaurasia B, Garg K, Deora H, Umana GE, Palmisciano P, et al. Molecular mechanisms of oxidative stress in stroke and cancer: review. Brain Disorders. 2022;5: 100029.CrossRef
62.
go back to reference Ghani RA, Abdul Malek NNN, Ashari NSM, Abdullah N. Pomegranate juice induced cell cycle arrest and apoptosis viamitochondrial pathway in human lung aden carcinoma A549 cells. Int J Eng Technol. 2018;7:287–92.CrossRef Ghani RA, Abdul Malek NNN, Ashari NSM, Abdullah N. Pomegranate juice induced cell cycle arrest and apoptosis viamitochondrial pathway in human lung aden carcinoma A549 cells. Int J Eng Technol. 2018;7:287–92.CrossRef
63.
go back to reference Yao S, Zhang G, Cao H, Song G, Li Z, Zhang W. Correlation between microRNA-21 and expression of Th17 and treg cells in microenvironment of rats with hepatocellular carcinoma. Asian Pac J Trop Med. 2015;8(9):762–5.PubMedCrossRef Yao S, Zhang G, Cao H, Song G, Li Z, Zhang W. Correlation between microRNA-21 and expression of Th17 and treg cells in microenvironment of rats with hepatocellular carcinoma. Asian Pac J Trop Med. 2015;8(9):762–5.PubMedCrossRef
64.
go back to reference Wang J, Chu Y, Xu M, Zhang X, Zhou Y. MiR-21 promotes cell migration and invasion of hepatocellular carcinoma by targeting KLF5. Oncol Lett. 2018;17:2221–7.PubMedPubMedCentral Wang J, Chu Y, Xu M, Zhang X, Zhou Y. MiR-21 promotes cell migration and invasion of hepatocellular carcinoma by targeting KLF5. Oncol Lett. 2018;17:2221–7.PubMedPubMedCentral
65.
go back to reference Zhang Z, Wooi-Loon NG, Wang P, Tian L, Werner E, Wang H, et al. MicroRNA-21 modulates the levels of reactive oxygen species by targeting SOD3 and TNFα. Cancer Res. 2012;72(18):4707–13.PubMedPubMedCentralCrossRef Zhang Z, Wooi-Loon NG, Wang P, Tian L, Werner E, Wang H, et al. MicroRNA-21 modulates the levels of reactive oxygen species by targeting SOD3 and TNFα. Cancer Res. 2012;72(18):4707–13.PubMedPubMedCentralCrossRef
66.
go back to reference Shi L, Chen J, Yang J, Pan T, Zhang S, Wang Z. MiR-21 protected human glioblastoma U87MG cells from chemotherapeutic drug temozolomide induced apoptosis by decreasing Bax/Bcl-2 ratio and caspase-3 activity. Brain Res. 2010;17(1352):255–64.CrossRef Shi L, Chen J, Yang J, Pan T, Zhang S, Wang Z. MiR-21 protected human glioblastoma U87MG cells from chemotherapeutic drug temozolomide induced apoptosis by decreasing Bax/Bcl-2 ratio and caspase-3 activity. Brain Res. 2010;17(1352):255–64.CrossRef
67.
go back to reference Wang L, Alcon A, Yuan H, Ho J, Li QJ, Martins-Green M. Cellular and molecular mechanisms of pomegranate juice-induced anti-metastatic effect on prostate cancer cells. Integr Biol. 2011;3:742–54.CrossRef Wang L, Alcon A, Yuan H, Ho J, Li QJ, Martins-Green M. Cellular and molecular mechanisms of pomegranate juice-induced anti-metastatic effect on prostate cancer cells. Integr Biol. 2011;3:742–54.CrossRef
68.
go back to reference Rostami Z, Khorashadizadeh M, Ghoncheh M, Naseri M. Effect of pomegranate extract in mesenchymal stem cells by modulation of microRNA-155, microRNA-21, microRNA-23b, microRNA-126a, and PI3K\AKT1\NF-κB expression. DNA Cell Biol. 2020;39(10):1779–88.PubMedCrossRef Rostami Z, Khorashadizadeh M, Ghoncheh M, Naseri M. Effect of pomegranate extract in mesenchymal stem cells by modulation of microRNA-155, microRNA-21, microRNA-23b, microRNA-126a, and PI3K\AKT1\NF-κB expression. DNA Cell Biol. 2020;39(10):1779–88.PubMedCrossRef
69.
go back to reference Niu J, Shi Y, Tan G, Yang CH, Fa M, Pfeffer IM, et al. DNA damage induces NF-κB-dependent microRNA-21 up-regulation and promotes breast cancer cell invasion. J Biol Chem. 2012;287:21783–95.PubMedPubMedCentralCrossRef Niu J, Shi Y, Tan G, Yang CH, Fa M, Pfeffer IM, et al. DNA damage induces NF-κB-dependent microRNA-21 up-regulation and promotes breast cancer cell invasion. J Biol Chem. 2012;287:21783–95.PubMedPubMedCentralCrossRef
70.
go back to reference Yang Y, Wang JK. The functional analysis of MicroRNAs involved in NF-κB signaling. Eur Rev Med Pharmacol Sci. 2016;20:1764–74.PubMed Yang Y, Wang JK. The functional analysis of MicroRNAs involved in NF-κB signaling. Eur Rev Med Pharmacol Sci. 2016;20:1764–74.PubMed
Metadata
Title
Pomegranate juice and punicalagin-mediated chemoprevention of hepatocellular carcinogenesis via regulating miR-21 and NF-κB-p65 in a rat model
Authors
Aya M. Hussein
Nadia M. El-Beih
Menha Swellam
Enas A. El-Hussieny
Publication date
01-12-2022
Publisher
BioMed Central
Published in
Cancer Cell International / Issue 1/2022
Electronic ISSN: 1475-2867
DOI
https://doi.org/10.1186/s12935-022-02759-9

Other articles of this Issue 1/2022

Cancer Cell International 1/2022 Go to the issue
Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras
Prof. Fabrice Barlesi
Developed by: Springer Medicine