We analysed the effects of small interfering RNA (siRNA)-mediated silencing of Apollon, a member of the inhibitors of apoptosis protein family, on the proliferative potential and ability of human breast cancer cell lines to undergo apoptosis. In wild-type p53 ZR75.1 cells, Apollon knockdown resulted in a marked, time-dependent decline of cell growth and an increased rate of apoptosis, which was associated with p53 stabilisation and activation of the mitochondrial-dependent apoptotic pathway. Pre-incubation of cells with a p53-specific siRNA resulted in a partial rescue of cell growth inhibition, as well as in a marked reduction of the apoptotic response, indicating p53 as a major player in cell growth impairment consequent on Apollon silencing. Apollon knockdown induced consistently less pronounced anti-proliferative and pro-apoptotic effects in mutant p53 MDA-MB-231 cells than in ZR75.1 cells. Furthermore, the activation of caspase-3 seemed to be essential for the induction of apoptosis after Apollon knockdown, as the Apollon-specific siRNA had no effect on the viability of caspase-3-deficient, wild-type p53 MCF-7 cells or the ZR75.1 cells after RNA interference-mediated caspase-3 silencing. Our results indicate that p53 stabilisation and caspase-3 activation concur to determine the apoptotic response mediated by Apollon knockdown in breast cancer cells, and suggest Apollon to be a potential new therapeutic target for this malignancy.
Lopergolo, A., Pennati, M., Gandellini, P., Orlotti, N., Poma, P., Daidone, M., et al. (2009). Apollon gene silencing induces apoptosis in breast cancer cells via p53 stabilisation and caspase-3 activation. BRITISH JOURNAL OF CANCER, 100(5), 739-746 [10.1038/sj.bjc.6604927].
Data di pubblicazione: | 2009 | |
Titolo: | Apollon gene silencing induces apoptosis in breast cancer cells via p53 stabilisation and caspase-3 activation | |
Autori: | ||
Citazione: | Lopergolo, A., Pennati, M., Gandellini, P., Orlotti, N., Poma, P., Daidone, M., et al. (2009). Apollon gene silencing induces apoptosis in breast cancer cells via p53 stabilisation and caspase-3 activation. BRITISH JOURNAL OF CANCER, 100(5), 739-746 [10.1038/sj.bjc.6604927]. | |
Rivista: | ||
Digital Object Identifier (DOI): | http://dx.doi.org/10.1038/sj.bjc.6604927 | |
Abstract: | We analysed the effects of small interfering RNA (siRNA)-mediated silencing of Apollon, a member of the inhibitors of apoptosis protein family, on the proliferative potential and ability of human breast cancer cell lines to undergo apoptosis. In wild-type p53 ZR75.1 cells, Apollon knockdown resulted in a marked, time-dependent decline of cell growth and an increased rate of apoptosis, which was associated with p53 stabilisation and activation of the mitochondrial-dependent apoptotic pathway. Pre-incubation of cells with a p53-specific siRNA resulted in a partial rescue of cell growth inhibition, as well as in a marked reduction of the apoptotic response, indicating p53 as a major player in cell growth impairment consequent on Apollon silencing. Apollon knockdown induced consistently less pronounced anti-proliferative and pro-apoptotic effects in mutant p53 MDA-MB-231 cells than in ZR75.1 cells. Furthermore, the activation of caspase-3 seemed to be essential for the induction of apoptosis after Apollon knockdown, as the Apollon-specific siRNA had no effect on the viability of caspase-3-deficient, wild-type p53 MCF-7 cells or the ZR75.1 cells after RNA interference-mediated caspase-3 silencing. Our results indicate that p53 stabilisation and caspase-3 activation concur to determine the apoptotic response mediated by Apollon knockdown in breast cancer cells, and suggest Apollon to be a potential new therapeutic target for this malignancy. | |
Settore Scientifico Disciplinare: | Settore BIO/14 - Farmacologia | |
Appare nelle tipologie: | 1.01 Articolo in rivista |
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