RT info:eu-repo/semantics/article
T1 Natural triterpenic diols promote apoptosis in astrocytoma cells through ROS-mediated mitochondrial depolarization and JNK activation
A1 Martín Martín, Rubén
A1 Ibeas, Elvira
A1 Carvalho Tavares, Juliana
A1 Hernández Garrido, Marita
A1 Ruiz Gutierrez, Valentina
A1 Nieto Callejo, María Luisa
K1 Triterpenic diols
K1 Dioles triterpénicos
K1 Apoptosis
K1 Astrocytoma cells
K1 Astrocitomas
K1 Mitochondrial depolarization
K1 Despolarización mitocondrial
AB 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.
PB PLOS ONE
SN 1932-6203
YR 2009
FD 2009
LK https://uvadoc.uva.es/handle/10324/47003
UL https://uvadoc.uva.es/handle/10324/47003
LA eng
NO PLoS ONE, 2009, vol. 4, n. 6. 14 p.
NO Producción Científica
DS UVaDOC
RD 22-nov-2024