A Diamine-PEGylated Oleanolic Acid Derivative Induced Efficient Apoptosis through a Death Receptor and Mitochondrial Apoptotic Pathway in HepG2 Human Hepatoma Cells
Hepatocellular carcinoma (HCC) is the most common type of liver cancer. Our recent studies have shown that the diamine-(PEG)ylated oleanolic acid (OADP) has strong anti-tumor effects in HCCs. In this study, we evaluated the anti-tumor mechanisms of OADP in the HepG2 HCC cell line. The cytotoxicity r...
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2020-09-01
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| Series: | Biomolecules |
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| author | Fatin Jannus Marta Medina-O’Donnell Francisco Rivas Luis Díaz-Ruiz Eva E. Rufino-Palomares José A. Lupiáñez Andrés Parra Fernando J. Reyes-Zurita |
| author_facet | Fatin Jannus Marta Medina-O’Donnell Francisco Rivas Luis Díaz-Ruiz Eva E. Rufino-Palomares José A. Lupiáñez Andrés Parra Fernando J. Reyes-Zurita |
| author_sort | Fatin Jannus |
| collection | DOAJ |
| description | Hepatocellular carcinoma (HCC) is the most common type of liver cancer. Our recent studies have shown that the diamine-(PEG)ylated oleanolic acid (OADP) has strong anti-tumor effects in HCCs. In this study, we evaluated the anti-tumor mechanisms of OADP in the HepG2 HCC cell line. The cytotoxicity results showed that HepG2 cell viability was markedly reduced, with a very low 50% of cell growth inhibitory concentration (IC<sub>50</sub>, 0.14 µg/mL). We then investigated the anti-tumor mechanisms of OADP in HepG2 cells. The flow-cytometry analysis was used to evaluate cell apoptosis, indicating that 74–95% of cells were apoptotic. OADP caused cell cycle arrest in the G0/G1 phase and the loss of the mitochondrial membrane potential (MMP). Western blot analysis was performed to assess the expression levels of key proteins associated with the underlying molecular mechanism. The results showed the clear upregulation of caspase-8, caspase-9, caspase-3, Bak, p21, and p53, accompanied by the downregulation of Bcl-2. Similar results were obtained by the cotreatment with OADP and the c-Jun N-terminal kinase (JNK) inhibitor SP600125. Agents such as OADP, which are capable of activating extrinsic and intrinsic apoptotic pathways, may represent potential HCC cancer therapies. |
| first_indexed | 2024-03-10T15:59:26Z |
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| issn | 2218-273X |
| language | English |
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| publishDate | 2020-09-01 |
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| series | Biomolecules |
| spelling | doaj.art-0ed901ac2f9b4dd2a1cac61c03bac6a32023-11-20T15:22:08ZengMDPI AGBiomolecules2218-273X2020-09-011010137510.3390/biom10101375A Diamine-PEGylated Oleanolic Acid Derivative Induced Efficient Apoptosis through a Death Receptor and Mitochondrial Apoptotic Pathway in HepG2 Human Hepatoma CellsFatin Jannus0Marta Medina-O’Donnell1Francisco Rivas2Luis Díaz-Ruiz3Eva E. Rufino-Palomares4José A. Lupiáñez5Andrés Parra6Fernando J. Reyes-Zurita7Department of Biochemistry and Molecular Biology I, Faculty of Sciences, University of Granada, Av. Fuentenueva 1, 18071 Granada, SpainDepartment of Organic Chemistry, Faculty of Sciences, University of Granada, Av. Fuentenueva 1, 18071 Granada, SpainDepartment of Organic Chemistry, Faculty of Sciences, University of Granada, Av. Fuentenueva 1, 18071 Granada, SpainDepartment of Biochemistry and Molecular Biology I, Faculty of Sciences, University of Granada, Av. Fuentenueva 1, 18071 Granada, SpainDepartment of Biochemistry and Molecular Biology I, Faculty of Sciences, University of Granada, Av. Fuentenueva 1, 18071 Granada, SpainDepartment of Biochemistry and Molecular Biology I, Faculty of Sciences, University of Granada, Av. Fuentenueva 1, 18071 Granada, SpainDepartment of Organic Chemistry, Faculty of Sciences, University of Granada, Av. Fuentenueva 1, 18071 Granada, SpainDepartment of Biochemistry and Molecular Biology I, Faculty of Sciences, University of Granada, Av. Fuentenueva 1, 18071 Granada, SpainHepatocellular carcinoma (HCC) is the most common type of liver cancer. Our recent studies have shown that the diamine-(PEG)ylated oleanolic acid (OADP) has strong anti-tumor effects in HCCs. In this study, we evaluated the anti-tumor mechanisms of OADP in the HepG2 HCC cell line. The cytotoxicity results showed that HepG2 cell viability was markedly reduced, with a very low 50% of cell growth inhibitory concentration (IC<sub>50</sub>, 0.14 µg/mL). We then investigated the anti-tumor mechanisms of OADP in HepG2 cells. The flow-cytometry analysis was used to evaluate cell apoptosis, indicating that 74–95% of cells were apoptotic. OADP caused cell cycle arrest in the G0/G1 phase and the loss of the mitochondrial membrane potential (MMP). Western blot analysis was performed to assess the expression levels of key proteins associated with the underlying molecular mechanism. The results showed the clear upregulation of caspase-8, caspase-9, caspase-3, Bak, p21, and p53, accompanied by the downregulation of Bcl-2. Similar results were obtained by the cotreatment with OADP and the c-Jun N-terminal kinase (JNK) inhibitor SP600125. Agents such as OADP, which are capable of activating extrinsic and intrinsic apoptotic pathways, may represent potential HCC cancer therapies.https://www.mdpi.com/2218-273X/10/10/1375triterpenesoleanolic acid(PEG)ylated oleanolic acidextrinsic apoptotic pathwayanti-tumor mechanismshepatocellular carcinoma |
| spellingShingle | Fatin Jannus Marta Medina-O’Donnell Francisco Rivas Luis Díaz-Ruiz Eva E. Rufino-Palomares José A. Lupiáñez Andrés Parra Fernando J. Reyes-Zurita A Diamine-PEGylated Oleanolic Acid Derivative Induced Efficient Apoptosis through a Death Receptor and Mitochondrial Apoptotic Pathway in HepG2 Human Hepatoma Cells Biomolecules triterpenes oleanolic acid (PEG)ylated oleanolic acid extrinsic apoptotic pathway anti-tumor mechanisms hepatocellular carcinoma |
| title | A Diamine-PEGylated Oleanolic Acid Derivative Induced Efficient Apoptosis through a Death Receptor and Mitochondrial Apoptotic Pathway in HepG2 Human Hepatoma Cells |
| title_full | A Diamine-PEGylated Oleanolic Acid Derivative Induced Efficient Apoptosis through a Death Receptor and Mitochondrial Apoptotic Pathway in HepG2 Human Hepatoma Cells |
| title_fullStr | A Diamine-PEGylated Oleanolic Acid Derivative Induced Efficient Apoptosis through a Death Receptor and Mitochondrial Apoptotic Pathway in HepG2 Human Hepatoma Cells |
| title_full_unstemmed | A Diamine-PEGylated Oleanolic Acid Derivative Induced Efficient Apoptosis through a Death Receptor and Mitochondrial Apoptotic Pathway in HepG2 Human Hepatoma Cells |
| title_short | A Diamine-PEGylated Oleanolic Acid Derivative Induced Efficient Apoptosis through a Death Receptor and Mitochondrial Apoptotic Pathway in HepG2 Human Hepatoma Cells |
| title_sort | diamine pegylated oleanolic acid derivative induced efficient apoptosis through a death receptor and mitochondrial apoptotic pathway in hepg2 human hepatoma cells |
| topic | triterpenes oleanolic acid (PEG)ylated oleanolic acid extrinsic apoptotic pathway anti-tumor mechanisms hepatocellular carcinoma |
| url | https://www.mdpi.com/2218-273X/10/10/1375 |
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