Issue 96, 2016, Issue in Progress

The oleanolic acid derivative, 3-O-succinyl-28-O-benzyl oleanolate, induces apoptosis in B16–F10 melanoma cells via the mitochondrial apoptotic pathway

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.

Graphical abstract: The oleanolic acid derivative, 3-O-succinyl-28-O-benzyl oleanolate, induces apoptosis in B16–F10 melanoma cells via the mitochondrial apoptotic pathway

Article information

Article type
Paper
Submitted
25 Jul 2016
Accepted
17 Sep 2016
First published
19 Sep 2016
This article is Open Access
Creative Commons BY license

RSC Adv., 2016,6, 93590-93601

The oleanolic acid derivative, 3-O-succinyl-28-O-benzyl oleanolate, induces apoptosis in B16–F10 melanoma cells via the mitochondrial apoptotic pathway

F. J. Reyes-Zurita, M. Medina-O'Donnell, R. M. Ferrer-Martin, E. E. Rufino-Palomares, S. Martin-Fonseca, F. Rivas, A. Martínez, A. García-Granados, A. Pérez-Jiménez, L. García-Salguero, J. Peragón, K. Mokhtari, P. P. Medina, A. Parra and J. A. Lupiáñez, RSC Adv., 2016, 6, 93590 DOI: 10.1039/C6RA18879F

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