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1,8 Cineole and Ellagic acid inhibit hepatocarcinogenesis via upregulation of MiR-122 and suppression of TGF-β1, FSCN1, Vimentin, VEGF, and MMP-9

PloS one, 2022-01, Vol.17 (1), p.e0258998-e0258998 [Peer Reviewed Journal]

2022 Abdallah et al. This is an open access article distributed under the terms of the Creative Commons Attribution License: http://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License. ;2022 Abdallah et al 2022 Abdallah et al ;ISSN: 1932-6203 ;EISSN: 1932-6203 ;DOI: 10.1371/journal.pone.0258998 ;PMID: 35081125

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Title:
1,8 Cineole and Ellagic acid inhibit hepatocarcinogenesis via upregulation of MiR-122 and suppression of TGF-β1, FSCN1, Vimentin, VEGF, and MMP-9
Author: Abdallah, Heba M I ; El Awdan, Sally A ; Abdel-Rahman, Rehab F ; Farrag, Abdel Razik H ; Allam, Rasha M
Kumar, Vikas
Subjects: Acids ; Angiogenesis ; Animals ; Antineoplastic Agents - pharmacology ; Arginase ; Biology and Life Sciences ; Carcinoma, Hepatocellular - chemically induced ; Carcinoma, Hepatocellular - drug therapy ; Carcinoma, Hepatocellular - metabolism ; Carcinoma, Hepatocellular - pathology ; Carrier Proteins - drug effects ; Carrier Proteins - metabolism ; Cineole ; Diethylnitrosamine ; Disease Models, Animal ; Doxorubicin ; Ellagic acid ; Ellagic Acid - administration & dosage ; Ellagic Acid - pharmacology ; Eucalyptol - administration & dosage ; Eucalyptol - pharmacology ; Ferritin ; Gelatinase B ; Gene expression ; Growth factors ; Hepatocellular carcinoma ; Humans ; Laboratory animals ; Liver ; Liver cancer ; Liver Neoplasms - chemically induced ; Liver Neoplasms - drug therapy ; Liver Neoplasms - metabolism ; Liver Neoplasms - pathology ; Markers ; Matrix metalloproteinase ; Matrix Metalloproteinase 9 - drug effects ; Matrix Metalloproteinase 9 - metabolism ; Matrix metalloproteinases ; Medicine and Health Sciences ; Mesenchyme ; Metalloproteinase ; Metastasis ; Microfilament Proteins - drug effects ; Microfilament Proteins - metabolism ; MicroRNAs - drug effects ; MicroRNAs - metabolism ; Pathogenesis ; Pharmacology ; Phosphatase ; Phytochemicals - pharmacology ; Proteins ; Rats ; Statistical analysis ; Transforming Growth Factor beta1 - drug effects ; Transforming Growth Factor beta1 - metabolism ; Transforming growth factor-b1 ; Tumor markers ; Tumors ; Vascular endothelial growth factor ; Vascular Endothelial Growth Factor A - drug effects ; Vascular Endothelial Growth Factor A - metabolism ; Vimentin ; Vimentin - drug effects ; Vimentin - metabolism ; α-Fetoprotein
Is Part Of: PloS one, 2022-01, Vol.17 (1), p.e0258998-e0258998
Description: Hepatocellular carcinoma (HCC) is one of the most burdened tumors worldwide, with a complex and multifactorial pathogenesis. Current treatment approaches involve different molecular targets. Phytochemicals have shown considerable promise in the prevention and treatment of HCC. We investigated the efficacy of two natural components, 1,8 cineole (Cin) and ellagic acid (EA), against diethylnitrosamine/2-acetylaminofluorene (DEN/2-AAF) induced HCC in rats. DEN/2-AAF showed deterioration of hepatic cells with an impaired functional capacity of the liver. In addition, the levels of tumor markers including alpha-fetoprotein, arginase-1, alpha-L-fucosidase, and ferritin were significantly increased, whereas the hepatic miR-122 level was significantly decreased in induced-HCC rats. Interestingly, treatment with Cin (100mg/kg) and EA (60mg/kg) powerfully restored these biochemical alterations. Moreover, Cin and EA treatment exhibited significant downregulation in transforming growth factor beta-1 (TGF-β1), Fascin-1 (FSCN1), vascular endothelial growth factor (VEGF), matrix metalloproteinase-9 (MMP-9), and epithelial-mesenchymal transition (EMT) key marker, vimentin, along with a restoration of histopathological findings compared to HCC group. Such effects were comparable to Doxorubicin (DOX) (2mg/kg); however, a little additive effect was evident through combining these phytochemicals with DOX. Altogether, this study highlighted 1,8 cineole and ellagic acid for the first time as promising phytochemicals for the treatment of hepatocarcinogenesis via regulating multiple targets.
Publisher: United States: Public Library of Science
Language: English
Identifier: ISSN: 1932-6203
EISSN: 1932-6203
DOI: 10.1371/journal.pone.0258998
PMID: 35081125
Source: Public Library of Science (PLoS) Journals Open Access
Geneva Foundation Free Medical Journals at publisher websites
MEDLINE
ProQuest Central
DOAJ Directory of Open Access Journals
PMC

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1,8 Cineole and Ellagic acid inhibit hepatocarcinogenesis via upregulation of MiR-122 and suppression of TGF-β1, FSCN1, Vimentin, VEGF, and MMP-9

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