Programmed cell death, also known as Apoptosis, is an active process occurring in
eukaryotic cells and it depends on various sets of pro and anti-apoptotic proteins.
Chemoprevention of colorectal cancer can be achieved by inducing apoptosis using synthetic
compound, Celecoxib and natural peptide, Dolastatin 15 in an effective manner. But
the apoptotic signaling by these two drugs remain unclear. The present study was thus
focused on the role of Bcl2- family of proteins and their interplay with p53 in rats
during the chemoprevention by these two drugs. After treatment for 6 weeks with 1,
2-dimethylhydrazine (DMH), animals showed a marked occurrence of multiple plaque lesions.
However, a simultaneous treatment with Celecoxib and Dolastatin 15 decreases such
number to a significant level. DMH treatment also decreases the number of apoptotic
cells in the colonic enterocytes which were corrected to the normal level by Celecoxib
and Dolastatin 15. An increased expression of Bcl2 while other proteins like Bax,
Apaf-1, cyt c and caspases in the apoptotic pathway, and the tumor suppressor proteins,
p53 and p21 get down-regulated after DMH treatment which were reverted back to normal
with Celecoxib and Dolastatin 15. Also, cells having high mitochondrial membrane potential
had been seen to increase to significant levels which were reduced after the administration
of these anti-inflammatory drugs. In silico molecular docking studies also showed
that Dolastatin 15 and Celecoxib may bind to the active site pocket of Bcl2, thus
revealing the direct target of Dolastatin 15 and Celecoxib apart from binding to COX-2.
