A Diamine-PEGylated Oleanolic Acid Derivative Induced Efficient Apoptosis through a Death Receptor and Mitochondrial Apoptotic Pathway in HepG2 Human Hepatoma Cells Jannus, Fatin Medina-O'Donnell, Marta Rivas Sánchez, Francisco De Asís Díaz Ruiz, Luis Rufino Palomares, Eva Lupiáñez Cara, José Antonio Parra Sánchez, Andrés Reyes Zurita, Fernando Jesús Triterpenes Oleanolic acid (PEG)ylated oleanolic acid Extrinsic apoptotic pathway Anti-tumor mechanisms Hepatocellular carcinoma 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 (IC50, 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. 2020-11-20T09:45:49Z 2020-11-20T09:45:49Z 2020 journal article Jannus F, Medina-O’Donnell M, Rivas F, Díaz-Ruiz L, Rufino-Palomares EE, Lupiáñez JA, Parra A, Reyes-Zurita FJ. A Diamine-PEGylated Oleanolic Acid Derivative Induced Efficient Apoptosis through a Death Receptor and Mitochondrial Apoptotic Pathway in HepG2 Human Hepatoma Cells. Biomolecules. 2020; 10(10):1375. [https://doi.org/10.3390/biom10101375] http://hdl.handle.net/10481/64390 10.3390/biom10101375 eng http://creativecommons.org/licenses/by/3.0/es/ open access Atribución 3.0 España MDPI