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2001). A number of cellular stressors such as: loss of survival factors, calcium overload,
drugs, irradiation and hypoxia ultimately lead to the changes in mitochondrial transition
potential (MTP) which will cause the release of cytochrome C, apoptosis-inducing factor
(AIF), SmaclDiablo and procaspases in to the cytosol. The loss of survival factors, such
as integrins, will result in the activation of MAPK and PI-3K pathways. The activation of
these pathways will result in the translocation of pro-apoptotic proteins, such as BAX,
from the cytoplasm to the outer mitochondrial membrane. The effects of radiation and
drug administration may cause the activation of p53 through an increased production of
free radicals which will also lead to the translocation of Bax. The activation of p53 was
also found to cause an increased expression of proapoptotic Bax and decreased
expression of anti apoptotic Bcl-2, which will tip the balance between the Bax and Bcl-2
towards the development of apoptosis (Miyashita et al. 1994; Miyashita and Reed 1995).
Translocation of Bax may also be caused by the effects of hypoxia, although the exact
mechanism through which this is achieved is not known (Saikumar et aI.1999).
The Bax protein is found to cause the changes in the MTP which will result in the
opening of the mitochondrial pores and a release of cytochrome C in the cytosol. The
release of cytochrome C is considered to be a critical step in the execution of apoptosis
(Regula et al. 2003). Once released from the mitochondria, cytochrome C combines with
apoptotic protease activating factor I (apafl), dADP and procaspase 9 resulting in the
formation of an apoptosis inducing complex-apoptosome. Formation of apoptosomes
causes the activation of caspase 9. Newly activated caspase 9 processes and activates
pro-capase 3 which will ultimately result in the degradation of cellular and nuclear
proteins. This is achieved by the activation of CAD, which causes the strand breaks in
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