Signal transduction pathways linking polyamines to apoptosis

Abstract

Polyamines are important multifunctional cellular components and are classically considered as mediators of cell growth and division. Recently polyamines have been also implicated in cell death. Now it appears that polyamines are bivalent regulators of cellular functions, promoting proliferation or cell death depending on the cell type and on environmental signals. This review draws a picture about the role of polyamines in signalling pathways related to apoptotic cell death and the proposed molecular targets of these polycations at the level of the apoptotic cascade. Solid evidence indicates that polyamines may affect the mitochondrial and postmitochondrial phases of apoptosis, by modulating cytochrome c release from mitochondria and activation of caspases. Recently, polyamines have been also implicated in the regulation of the premitochondrial phase of apoptosis, during which upstream apoptotic signal transduction pathways are activated. The studies reviewed here suggest that polyamines may participate in loops involving interaction with signal transduction pathways and activation/expression of proteins that may control cell death or cell growth.

Ornithine decarboxylase activity in tumor cell lines correlates with sensitivity to cell death induced by histone deacetylase inhibitors

“…Additionally, ODC is induced in response to some death signals, and polyamines regulate apoptosis by modulating the activation or expression of several apoptotic proteins (39). We found that TSA induced ODC expression and activity in cell lines that were sensitive to the apoptotic effects of HDAC inhibitors.…”

“…This suggests that polyamines affect the apoptotic response of tumor cells treated with HDAC inhibitors. Polyamine depletion in tumor cells also alters the response to other chemotherapeutic agents, depending on the apoptotic stimulus and cell type (39). For example, polyamine-depleted IEC-6 rat intestinal epithelial cells show increased susceptibility to apoptosis induced by staurosporin but are protected from apoptosis induced by tumor necrosis factor-a or camptothecin (40,41).…”

Polyamines and transglutaminases: future perspectives

“…Cellular polyamine concentrations are highly regulated. Intracellular accumulation of polyamines, due to either high extracellular levels or deregulation of the systems that control polyamine homeostasis, can induce programmed cell death (or apoptosis) in various cell types (Tobias and Kahana 1995;Pignatti et al 2004;Seiler and Raul 2005). Therefore, maintenance of the proper concentration of polyamines is necessary for above functions, whereas excess in their levels could lead to toxicity Amendola et al 2009;Pegg 2013).…”

Polyamines and transglutaminases: biological, clinical, and biotechnological perspectives

“…Intracellular accumulation of polyamines, due either to high extracellular levels or deregulation of the systems that control polyamine homeostasis, can induce programmed cell death (or apoptosis) in various cell types (Tobias and Kahana 1995;Pignatti et al 2004;Seiler and Raul 2005). The natural polyamines spermidine and spermine are substrates of several enzymes that generate cytotoxic metabolites: monoamine oxidase (MAO), polyamine oxidase (PAO), spermine oxidase (SMO), and copper amine oxidases (CuAOs) Agostinelli et al 2004).…”