23-Hydroxyursolic Acid Isolated from the Stem Bark of

التفاصيل البيبلوغرافية
العنوان: 23-Hydroxyursolic Acid Isolated from the Stem Bark of
المؤلفون: Jong-Heon, Won, Kyung-Sook, Chung, Eun-Young, Park, Jeong-Hun, Lee, Jung-Hye, Choi, Leon Azefack, Tapondjou, Hee-Juhn, Park, Masaaki, Nomura, Ahmed H E, Hassan, Kyung-Tae, Lee
المصدر: Molecules
سنة النشر: 2018
مصطلحات موضوعية: Membrane Potential, Mitochondrial, Caspase 8, Death Domain Receptor Signaling Adaptor Proteins, Plant Stems, caspase, apoptosis, death-inducing signaling complex, HL-60 Cells, Models, Biological, Triterpenes, Article, Mitochondria, Leukemia, Promyelocytic, Acute, Plant Bark, Humans, Bcl-2, fas Receptor, Araliaceae, 23-hydroxyursolic acid, Cell Proliferation
الوصف: The natural product 23-hydroxyursolic acid (23-HUA) is a derivative of ursolic acid, which is known to induce cancer cell apoptosis. However, apoptotic effects and mechanisms of 23-HUA have not been well characterized yet. Herein, we investigated the molecular mechanisms of 23-HUA-induced apoptosis in HL-60 human promyelocytic leukemia cells. 23-HUA-treated HL-60 cells showed apoptotic features including internucleosomal DNA condensation and fragmentation as well as externalization of phosphatidylserine residues. 23-HUA induced a series of mitochondrial events including disruption of mitochondrial membrane potential (ΔΨm), cytochrome c and Smac/DIABLO release and loss of balance between pro-apoptotic and anti-apoptotic Bcl-2 proteins in HL-60 cells. In addition, 23-HUA activated caspase-8, caspase-9 and caspase-3. Pretreatment with a broad caspase inhibitor (z-VAD-fmk), a caspase-3 inhibitor (z-DEVD-fmk), and a caspase-8 inhibitor (z-IETD-fmk) significantly attenuated 23-HUA-induced DNA fragmentation. After 23-HUA-induced apoptosis, proteins expression levels of FasL, Fas and FADD constituting the death-inducing signaling complex (DISC) were upregulated in HL-60 cells. Moreover, transfection with Fas or FADD siRNA significantly blocked 23-HUA-induced DNA fragmentation and caspases activation. Taken together, these findings indicate that 23-HUA induces apoptosis in HL-60 human promyelocytic leukemia cells through formation of DISC and caspase-8 activation leading to loss of ΔΨm and caspase-3 activation.
تدمد: 1420-3049
URL الوصول: https://explore.openaire.eu/search/publication?articleId=pmid________::c09aa722af505684b0d29684b7289a13
https://pubmed.ncbi.nlm.nih.gov/30551620
Rights: OPEN
رقم الانضمام: edsair.pmid..........c09aa722af505684b0d29684b7289a13
قاعدة البيانات: OpenAIRE