RT Journal Article
T1 The oleanolic acid derivative, 3-O-succinyl-28-O-benzyl oleanolate, induces apoptosis in B16-F10 melanoma cells via the mitochondrial apoptotic pathway
A1 Reyes-Zurita, Fernando J.
A1 Medina-O'Donnell, Marta
A1 Ferrer-Martin, Rosa M.
A1 Rufino-Palomares, Eva E.
A1 Martin-Fonseca, Samuel
A1 Rivas, Francisco
A1 Martinez, Antonio
A1 Garcia-Granados, Andres
A1 Perez-Jimenez, Amalia
A1 Garcia-Salguero, Leticia
A1 Peragon, Juan
A1 Mokhtari, Khalida
A1 Medina, Pedro P.
A1 Parra, Andres
A1 Lupianez, Jose A.
K1 Gilthead sea bream
K1 Protein-turnover rates
K1 Colon-cancer cells
K1 Maslinic acid
K1 Natural triterpene
K1 Sparus-aurata
K1 Adenocarcinoma cells
K1 Betulinic acid
K1 White muscle
K1 Growth
AB Oleanolic acid (1) is a pentacyclic triterpene present in olive pomace, which is known to induce apoptosis and to have anti-tumor properties; however, high concentrations of this product are necessary to produce cytotoxic effects. The 3-O-succinyl-28-O-benzyl oleanolate derivative (4) presents greater cytotoxicity and apoptosis effects than its natural precursor, oleanolic acid, or its benzyl derivative (2). This study examines the response of B16-F10 melanoma cells to treatment with compound 4, in comparison to 1 and 3. Our studies show that treatment with 4 results in a significant inhibition of cell proliferation in a dose-dependent manner and causes apoptotic cell death. At concentrations inhibiting cell growth by 50% and 80%, compound 4 induces strong G(0)/G(1) cell-cycle arrest, around 72-95% apoptosis, and mitochondrial disturbances confirmed by FACS analysis, which probably involve the activation of the intrinsic apoptotic route. Morphological changes including cell shrinkage, chromatin condensation, and loss of nuclear architecture were also observed. In this report, we demonstrated for the first time that in melanoma cancer cells, compound 4 exerts a significant anti-proliferation effect by inducing the apoptotic process with mitochondrial depolarization. These findings support the role of compound 4 as a new, potential therapeutic tool against aberrant cell proliferation in melanoma.
PB Royal soc chemistry
SN 2046-2069
YR 2016
FD 2016-01-01
LK http://hdl.handle.net/10668/18916
UL http://hdl.handle.net/10668/18916
LA en
DS RISalud
RD Apr 12, 2025