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Please use this identifier to cite or link to this item: http://hdl.handle.net/10481/45624

Title: The oleanolic acid derivative, 3-O-succinyl-28-O-benzyl oleanolate, induces apoptosis in B16–F10 melanoma cells via the mitochondrial apoptotic pathway
Authors: Reyes Zurita, Fernando Jesús
Medina-O'Donnell, Marta
Ferrer-Martín, Rosa María
Rufino Palomares, Eva Encarnación
Martín-Fonseca, Samuel
Rivas, Francisco
Martínez, Antonio
García Granados López de Hierro, Andrés
Pérez-Jiménez, Amalia
García-Salguero, Leticia
Peragón Sánchez, Juan
Mokhtari, Khalida
Medina, Pedro P.
Parra Sánchez, Andrés
Lupiáñez Cara, José Antonio
Issue Date: 2016
Abstract: 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 G0/G1 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.
Sponsorship: This study was supported by grants Group BIO 157 from the Technology and Innovation Council of the Andalucian regional government and AGL2006-12210-C03-02/ALI, SAF2005-01627, ISCIII-RTICC (RD06/0020/0046) from the Spanish government and European Union FEDER funds.
Publisher: Royal Society of Chemistry
Keywords: Oleanolic acid
Melanoma
Treatment
Olive pomace
Apoptosis
Antineoplastic agents
Triterpenoid
Therapeutics
URI: http://hdl.handle.net/10481/45624
ISSN: 2046-2069
Citation: Reyes-Zurita, F.J.; et al. The oleanolic acid derivative, 3-O-succinyl-28-O-benzyl oleanolate, induces apoptosis in B16–F10 melanoma cells via the mitochondrial apoptotic pathway. RSC Advances, 6: 93590-93601 (2016). [http://hdl.handle.net/10481/45624]
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