Production Of Anti Apoptotic Proteins By Cancer Cells

3411 words - 14 pages

Apoptosis is a form of cell death which is an essential process for growth and development of multi cellular organism and removes damaged cells to prevent inflammation (Madeo, Frohlich et al. 1997). In addition, apoptosis can be morphologically characterized by cell shrinkage, chromatin condensation, and formation of apoptotic complex (Madeo, Frohlich et al. 1997,Qi, Kim, et al. 2013).The main biochemical characteristics of apoptosis include caspase activation and DNA fragmentation (Madeo, Frohlich et al. 1997, Du, Fang et al. 2000). Apoptosis is induced by various physiological or toxic signals such as chemotherapeutics, DNA damage, ultraviolet irradiation, oxidative stress and endoplasmic reticulum stress. Impaired cell death is a characteristic of cancer cells, determining their resistance to apoptotic signals, (Adams and Cory 2007, Hartman and Czyz 2013) which is one of the six essential alterations in cell biological capabilities acquired during the multistep development of human tumours (Hanahan and Weinberg 2011, Hartman and Czyz 2013) and remains critical in effective cancer treatment strategies (Adams and Cory 2007).
Two major apoptotic paths have been defined; death receptor (extrinsic) and mitochondrial (intrinsic) pathway and they are usually switched on in a stimulus-dependent manner (Steel, Doherty et al. 2004, Adams and Cory 2007, Hartman and Czyz 2013).Such that extra-cellular death inducing signals via Fas receptors and various intra cellular signals result in activation of caspases (Du, Fang et al. 2000) (caspase 8 and 9) respectively. Intrinsic apoptotic pathway is widely implicated as a barrier to cancer pathogenesis than extrinsic apoptosis pathway (Hanahan and Weinberg 2011).
In order to understand anti-apoptotic protein expression and their importance in cancer cells, it is required to identify molecular interactions of anti-apoptotic proteins with apoptotic cascade members and their stimuli. Previous studies based on this specific area have been lead to recognize potential therapeutic targets by restoring cell death mechanism via apoptosis in malignant cells.
Several families of proteins directly or indirectly influence different steps of the apoptosis pathway. Recognized regulators include Bcl-2 family of proteins, inhibitors of apoptosis (IAPs) (Desagher, Sand et al. 1999, Du, Fang et al. 2000, Czabotar et al. 2008, Hartman and Czyz 2013)and Heat shock proteins (HSPs) (Garrido, Bruey et al. 1999, Beere 2004, Steel, Doherty et al. 2004). With respect to Bcl-2 family mediated apoptosis control, counterbalancing pro- and anti-apoptotic members of the Bcl-2 family of apoptotic regulatory proteins provide the ultimate signal towards apoptosis. Pro-survival sub family members are also known as anti-apoptotic proteins, Bcl-xL, Bcl-w, Mcl-1, A1 act as inhibitors of Bax and Bak proteins. When Bax and Bak are separated by their anti-apoptotic members, integrity of mitochondrial outer membrane is disrupted and pro-apoptotic...

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