Apollon gene silencing induces apoptosis in breast cancer cells through p53 stabilisation and caspase-3 activation

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.

Apoptotic Mediators are Upregulated in the Skeletal Muscle of Chronic/Progressive Mouse Model of Parkinson's Disease

“…To our knowledge, these are the first data to demonstrate the PD-induced alterations in p53 expression in gastrocnemius muscle. P53 has been reported to induce apoptosis by caspase activation eventually leading to the cleavage and the subsequent activation of caspase-3 (Lopergolo et al, 2009;Nigam et al, 2009;Pratheeshkumar et al, 2010;Chan et al, 2010;Son et al, 2010;Choi et al, 2010;Pratheeshkumar et al, 2012). Thus, to further investigate the occurrence of apoptosis in gastrocnemius muscle, we tested the alterations in active caspase-3 expression following the induction of PD.…”

BIRC6 promotes hepatocellular carcinogenesis: Interaction of BIRC6 with p53 facilitating p53 degradation

“…Given that p53, a critical molecular in regulating tumor proliferation and apoptosis, is closely related to IAPs. 10,11 We determined the p53 expression in these cells. It is evident that BIRC6 knockdown significantly increased the protein levels of endogenous p53, but did not change the mRNA levels of endogenous p53 (Figs.…”

“…9 Notably, previous studies have found that p53 is a key downstream effector of BIRC6. 10,11 However, it is unclear whether BIRC6 can interact with p53, and in which way BIRC6 regulates p53. Meanwhile, the role of such association in HCC carcinogenesis remains unknown.…”

“…10,[12][13][14][15][16][17][18] BIRC6 was identified as a novel intervention target for neuroblastoma therapy. 19 Importantly, excessive expression of BIRC6 is significantly correlated with unfavorable clinical features at diagnosis, pathological classification, high cellular proliferation and poor prognosis in cancers.…”

The expression BIRC6 gene in patients with chronic lymphocytic leukemia – a preliminary study

“…The regulation of Bruce protein expression plays an important role in apoptosis, as an increase or decrease in this protein expression changes the cell susceptibility to a death stimulus. Thus, understanding BIRC6 gene expression is perceived as being a new therapeutic aim in the treatment of malignancies characterized by its over-expression [24,17].…”