Survivin as a target for new anticancer interventions

Abstract

Survivin is a member of the inhibitor of apoptosis protein (IAP) family, that has been implicated in both control of cell division and inhibition of apoptosis. Specifically, its anti-apoptotic function seems to be related to the ability to directly or indirectly inhibit caspases. Survivin is selectively expressed in the most common human neoplasms and appears to be involved in tumor cell resistance to some anticancer agents and ionizing radiation. On the basis of these findings survivin has been proposed as an attractive target for new anticancer interventions. Several preclinical studies have demonstrated that down-regulation of survivin expression/function, accomplished through the use of antisense oligonucleotides, dominant negative mutants, ribozymes, small interfering RNAs and cyclin-dependent kinase inhibitors, increased the apoptotic rate, reduced tumor-growth potential and sensitized tumor cells to chemotherapeutic drugs with different action mechanisms and γ-irradiation in in vitro and in vivo models of different human tumor types.

siRNA-mediated Silencing of Survivin Inhibits Proliferation and Enhances Etoposide Chemosensitivity in Acute Myeloid Leukemia Cells

“…Overexpression of survivin, a member of the IAP family of proteins, is attributed to the chemoresistance of tumor cells (Adida et al, 2000;Fukuda and Pelus, 2006;Ryan et al, 2009;Feng et al, 2013). On the contrary, different studies have shown that suppression of survivin expression can sensitize tumor cells to anti-cancer drugs (Zaffaroni et al, 2005). In the current study to investigate whether down-regulation of survivin affects chemosensitivity in AML cells, we examined the effect of survivin specific siRNA and etoposide alone or in combination on HL-60 AML cells.…”

“…Furthermore, survivin is required for stabilization of spindle microtubules and accurate chromosome segregation during mitosis. However, the exact roles of survivin in regulation of cell division and apoptosis are still unclear (Zaffaroni and Daidone, 2002;Zaffaroni et al, 2005;Kelly et al, 2011;Church and Talbot, 2012).…”

“…Because of this overexpression in cancer, its important role in apoptosis as well as cell division, and its association with drug resistance, survivin has been considered as an attractive therapeutic target in malignancies (Ryan et al, 2009;Feng et al, 2013). Various studies have shown that suppression of survivin expression with dominant negative mutants, ribozymes, antisense oligonucleotides (ASOs) and small interfering RNAs (siRNAs) increased spontaneous apoptosis and sensitized tumor cells to chemotherapy and ionizing radiation (Zaffaroni et al, 2005;Ryan et al, 2009). Yet, a study on whether the siRNA targeting of survivin could enhance the sensitivity of AML cells to antileukemic agent etoposide has not been investigated until now.…”

CDC20, a potential cancer therapeutic target, is negatively regulated by p53

“…In fact, Survivin that is suppressed by p53 is highly expressed in various cancer tissues and specific inhibitors for it are developed for clinical application (Zaffaroni et al, 2005). Since we have been analysing gene expression profiles of various cancer tissues using cDNA microarray, we compared the gene expression profile data for cells in which p53 gene was exogenously introduced and those for various clinical cancers.…”

Hyaluronan oligosaccharides sensitize lymphoma resistant cell lines to vincristine by modulating P‐glycoprotein activity and PI3K/Akt pathway

“…However, several reports have demonstrated its expression in human tumors and enhanced survivin levels have been correlated with tumor progression. 6 Besides, it has been recently shown that Akt may regulate survivin expression in neuroblastoma. 7 Hyaluronan (HA) is a large, linear glycosaminoglycan with a molecular weight ranging from 10 5 to 10 7 Da.…”