Apoptosis is a synchronized procedure of cell death that is regulated by
caspases and proapoptotic
proteins. During apoptosis, translocation of
cytochrome c, an electron carrier, from mitochondria into the cytosol is regulated by Bcl-2 family members.
Cytochrome c in association with an apoptotic
protease activating factor (Apaf), a proapoptotic
protein essential for cell differentiation and
procaspase-9 form the
apoptosome complex, which consecutively activates effector
caspase,
caspase-3, and coordinate the implementation of apoptosis. In the current study, an attempt has been made to gain insight into
piroxicam, a traditional nonsteroidal antiinflammatory drug and
c-phycocyanin, a biliprotein from Spirulina platensis (cyanobacterium) mediated apoptosis in
DMH-induced
colon cancer. Male Sprague-Dawley rats were segregated into 5 groups: control,
DMH,
DMH +
piroxicam,
DMH +
c-phycocyanin, and
DMH +
piroxicam +
c-phycocyanin. Results illustrated that
piroxicam and
c-phycocyanin treatments stimulate
cytochrome c release by downregulating the Bcl-2 (an antiapoptotic
protein) expression significantly, while promoting the level of Bax (a proapoptotic
protein), thereby activating
caspases (caspases-9 and -3) and Apaf-1. The outcomes of the present study clearly signify that
piroxicam and
c-phycocyanin may mediate mitochondrial-dependent apoptosis in
DMH-induced
colon cancer. Moreover, apoptosis induction was more apparent in the combination regimen of
piroxicam and
c-phycocyanin than the individual drugs alone.