2026-05-05T21:47:35Zhttps://uvadoc.uva.es/oai/request

oai:uvadoc.uva.es:10324/470032021-06-23T09:53:32Zcom_10324_1134com_10324_931com_10324_894col_10324_1213

Martín Martín, Rubén Ibeas, Elvira Carvalho Tavares, Juliana Hernández Garrido, Marita Ruiz Gutierrez, Valentina Nieto Callejo, María Luisa 2021-06-22T11:52:12Z 2021-06-22T11:52:12Z 2009 PLoS ONE, 2009, vol. 4, n. 6. 14 p. 1932-6203 https://uvadoc.uva.es/handle/10324/47003 10.1371/journal.pone.0005975 Producción Científica Background: Triterpene alcohols and acids are multifunctional compounds widely distributed throughout the plant kingdom that exhibit a variety of beneficial health properties, being synthetic analogs of oleanolic acid under clinical evaluation as anti-tumoral therapeutic agents. However, the antineoplastic activity of two natural occuring triterpenoid alcohols extracted from olive oil, erythrodiol (an intermediate from oleanolic acid), and its isomer, uvaol, has barely been reported, particularly on brain cancer cells. Astrocytomas are among the most common and aggressive type of primary malignant tumors in the neurological system lacking effective treatments, and in this study, we addressed the effect of these two triterpenic diols on the human 1321N1 astrocytoma cell line. Principal Findings: Erythrodiol and uvaol effectively affected cell proliferation, as well as cell cycle phases and induced 1321N1 cell death. Both triterpenes successfully modulated the apoptotic response, promoting nuclear condensation and fragmentation. They caused retraction and rounding of cultured cells, which lost adherence from their supports, while F-actin and vimentin filaments disappeared as an organized cytoplasmic network. At molecular level, changes in the expression of surface proteins associated with adhesion or death processes were also observed. Moreover, triterpene exposure resulted in the production of reactive oxygen species (ROS) with loss of mitochondrial transmembrane potential, and correlated with the activation of c-Jun N-terminal kinases (JNK). The presence of catalase reversed the triterpenic diols-induced mitochondrial depolarization, JNK activation, and apoptotic death, indicating the critical role of ROS in the action of these compounds. Conclusions: Overall, we provide a significant insight into the anticarcinogenic action of erythrodiol and uvaol that may have a potential in prevention and treatment of brain tumors and other cancers. Ministerio de Ciencia e Innovación (grants SAF2005-01242, SAF2008-00245 and AGL2008-022845) Junta de Castilla y León (grant CSI11A08) application/pdf eng PLOS ONE info:eu-repo/semantics/openAccess http://creativecommons.org/licenses/by-nc-nd/4.0/ © 2009 PLOS Attribution-NonCommercial-NoDerivatives 4.0 Internacional Triterpenic diols Dioles triterpénicos Apoptosis Astrocytoma cells Astrocitomas Mitochondrial depolarization Despolarización mitocondrial Natural triterpenic diols promote apoptosis in astrocytoma cells through ROS-mediated mitochondrial depolarization and JNK activation info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0005975 SI