Anticancer potential of eugenol in hepatocellular carcinoma through modulation of oxidative stress, inflammation, apoptosis, and proliferation mechanisms
Abstract This investigation explored the chemopreventive effects of eugenol on diethylnitrosamine (DENA) and acetylaminofluorene (AAF)-induced hepatocellular carcinoma (HCC) in Wistar rats. To induce HCC, DENA was administered intraperitoneally once per week for two weeks at a concentration of 150 m...
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Springer
2025-06-01
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| Series: | Discover Oncology |
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| Online Access: | https://doi.org/10.1007/s12672-025-02243-6 |
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| author | Mohamed Y. Zaky Hadeer M. Morsy Adel Abdel-Moneim Khairy M. A. Zoheir Anthony Bragoli Mostafa A. Abdel-Maksoud Abdulaziz Alamri Osama M. Ahmed |
| author_facet | Mohamed Y. Zaky Hadeer M. Morsy Adel Abdel-Moneim Khairy M. A. Zoheir Anthony Bragoli Mostafa A. Abdel-Maksoud Abdulaziz Alamri Osama M. Ahmed |
| author_sort | Mohamed Y. Zaky |
| collection | DOAJ |
| description | Abstract This investigation explored the chemopreventive effects of eugenol on diethylnitrosamine (DENA) and acetylaminofluorene (AAF)-induced hepatocellular carcinoma (HCC) in Wistar rats. To induce HCC, DENA was administered intraperitoneally once per week for two weeks at a concentration of 150 mg/kg body weight (b.w.), followed by oral AAF administration for 3 weeks, four times a week, at a dosage of 20 mg/kg b.w. After these three weeks, the rats were treated with eugenol every other day for 17 weeks at a dosage of 20 mg/kg b.w. In vitro, eugenol reduced cell viability (IC50 of 189.29 µg/mL) and inhibited cell migration in the HCC cell line HepG2. Moreover, eugenol treatment in DENA/AAF-induced rats significantly improved cancerous histopathological changes and reduced inflammatory cell infiltration in the liver. Eugenol treatment significantly reduced the activity levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), and alkaline phosphatase (ALP), along with the levels of total bilirubin (TBIL), alpha-fetoprotein (AFP), carcinoembryonic antigen (CEA), carbohydrate antigen 19–9 (CA 19–9), lipid peroxides (LPO), tumor necrosis factor-α (TNF-α), and interleukin-1β (IL-1β). Additionally, the expressions of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), interleukin-8, C-X-C Motif Chemokine Receptor 3 (CXCR3), B-cell lymphoma 2 (Bcl-2), IQ Motif Containing GTPase Activating Protein 1 (IQGAP1), IQ Motif Containing GTPase Activating Protein 3 (IQGAP3), Harvey rat sarcoma viral oncogene homolog (HRAS), Kirsten rat sarcoma viral oncogene homolog (KRAS), and Ki-67 were downregulated following eugenol administration in DENA/AAF-induced HCC. Conversely, eugenol supplementation significantly enhanced glutathione (GSH) content, as well as the activities of glutathione peroxidase (GPx) and superoxide dismutase (SOD), and the levels of nuclear factor erythroid 2-related factor 2 (Nrf2). Furthermore, the expressions of tumor suppressor gene p53, Bcl-2-associated X protein (BAX), death receptor 4 (DR4), death receptor 5 (DR5), decoy receptor 1 (DcR1), programmed cell death 5 (PDCD5), and IQ Motif Containing GTPase Activating Protein 2 (IQGAP2) were markedly upregulated compared to the DENA/AAF-administered group. These findings indicate that the potent anticancer effects of eugenol are primarily driven by its ability to reduce oxidative stress, suppress inflammation, and inhibit cell proliferation while promoting apoptosis. This study underscores the potential of eugenol as a promising therapeutic agent for the prevention and management of HCC, offering a novel approach to HCC treatment. |
| format | Article |
| id | doaj-art-3da452d3cc0e4110a3249fdd2df05330 |
| institution | OA Journals |
| issn | 2730-6011 |
| language | English |
| publishDate | 2025-06-01 |
| publisher | Springer |
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| series | Discover Oncology |
| spelling | doaj-art-3da452d3cc0e4110a3249fdd2df053302025-08-20T02:10:34ZengSpringerDiscover Oncology2730-60112025-06-0116112010.1007/s12672-025-02243-6Anticancer potential of eugenol in hepatocellular carcinoma through modulation of oxidative stress, inflammation, apoptosis, and proliferation mechanismsMohamed Y. Zaky0Hadeer M. Morsy1Adel Abdel-Moneim2Khairy M. A. Zoheir3Anthony Bragoli4Mostafa A. Abdel-Maksoud5Abdulaziz Alamri6Osama M. Ahmed7Molecular Physiology Division, Zoology Department, Faculty of Science, Beni-Suef UniversityMolecular Physiology Division, Zoology Department, Faculty of Science, Beni-Suef UniversityMolecular Physiology Division, Zoology Department, Faculty of Science, Beni-Suef UniversityCell Biology Department, Biotechnology Research Institute, National Research CentreDepartment of Immunology, University of Pittsburgh School of MedicineBiochemistry Department, College of Science, King Saud UniversityBiochemistry Department, College of Science, King Saud UniversityMolecular Physiology Division, Zoology Department, Faculty of Science, Beni-Suef UniversityAbstract This investigation explored the chemopreventive effects of eugenol on diethylnitrosamine (DENA) and acetylaminofluorene (AAF)-induced hepatocellular carcinoma (HCC) in Wistar rats. To induce HCC, DENA was administered intraperitoneally once per week for two weeks at a concentration of 150 mg/kg body weight (b.w.), followed by oral AAF administration for 3 weeks, four times a week, at a dosage of 20 mg/kg b.w. After these three weeks, the rats were treated with eugenol every other day for 17 weeks at a dosage of 20 mg/kg b.w. In vitro, eugenol reduced cell viability (IC50 of 189.29 µg/mL) and inhibited cell migration in the HCC cell line HepG2. Moreover, eugenol treatment in DENA/AAF-induced rats significantly improved cancerous histopathological changes and reduced inflammatory cell infiltration in the liver. Eugenol treatment significantly reduced the activity levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), and alkaline phosphatase (ALP), along with the levels of total bilirubin (TBIL), alpha-fetoprotein (AFP), carcinoembryonic antigen (CEA), carbohydrate antigen 19–9 (CA 19–9), lipid peroxides (LPO), tumor necrosis factor-α (TNF-α), and interleukin-1β (IL-1β). Additionally, the expressions of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), interleukin-8, C-X-C Motif Chemokine Receptor 3 (CXCR3), B-cell lymphoma 2 (Bcl-2), IQ Motif Containing GTPase Activating Protein 1 (IQGAP1), IQ Motif Containing GTPase Activating Protein 3 (IQGAP3), Harvey rat sarcoma viral oncogene homolog (HRAS), Kirsten rat sarcoma viral oncogene homolog (KRAS), and Ki-67 were downregulated following eugenol administration in DENA/AAF-induced HCC. Conversely, eugenol supplementation significantly enhanced glutathione (GSH) content, as well as the activities of glutathione peroxidase (GPx) and superoxide dismutase (SOD), and the levels of nuclear factor erythroid 2-related factor 2 (Nrf2). Furthermore, the expressions of tumor suppressor gene p53, Bcl-2-associated X protein (BAX), death receptor 4 (DR4), death receptor 5 (DR5), decoy receptor 1 (DcR1), programmed cell death 5 (PDCD5), and IQ Motif Containing GTPase Activating Protein 2 (IQGAP2) were markedly upregulated compared to the DENA/AAF-administered group. These findings indicate that the potent anticancer effects of eugenol are primarily driven by its ability to reduce oxidative stress, suppress inflammation, and inhibit cell proliferation while promoting apoptosis. This study underscores the potential of eugenol as a promising therapeutic agent for the prevention and management of HCC, offering a novel approach to HCC treatment.https://doi.org/10.1007/s12672-025-02243-6Hepatocellular carcinomaDiethylnitrosamineAcetylaminofluoreneEugenolOxidative stress |
| spellingShingle | Mohamed Y. Zaky Hadeer M. Morsy Adel Abdel-Moneim Khairy M. A. Zoheir Anthony Bragoli Mostafa A. Abdel-Maksoud Abdulaziz Alamri Osama M. Ahmed Anticancer potential of eugenol in hepatocellular carcinoma through modulation of oxidative stress, inflammation, apoptosis, and proliferation mechanisms Discover Oncology Hepatocellular carcinoma Diethylnitrosamine Acetylaminofluorene Eugenol Oxidative stress |
| title | Anticancer potential of eugenol in hepatocellular carcinoma through modulation of oxidative stress, inflammation, apoptosis, and proliferation mechanisms |
| title_full | Anticancer potential of eugenol in hepatocellular carcinoma through modulation of oxidative stress, inflammation, apoptosis, and proliferation mechanisms |
| title_fullStr | Anticancer potential of eugenol in hepatocellular carcinoma through modulation of oxidative stress, inflammation, apoptosis, and proliferation mechanisms |
| title_full_unstemmed | Anticancer potential of eugenol in hepatocellular carcinoma through modulation of oxidative stress, inflammation, apoptosis, and proliferation mechanisms |
| title_short | Anticancer potential of eugenol in hepatocellular carcinoma through modulation of oxidative stress, inflammation, apoptosis, and proliferation mechanisms |
| title_sort | anticancer potential of eugenol in hepatocellular carcinoma through modulation of oxidative stress inflammation apoptosis and proliferation mechanisms |
| topic | Hepatocellular carcinoma Diethylnitrosamine Acetylaminofluorene Eugenol Oxidative stress |
| url | https://doi.org/10.1007/s12672-025-02243-6 |
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