Uncontrolled cell proliferation is the hallmark of cancer, and cancer cells have 
typically acquired damage to genes that directly regulate their cell cycles. The 
synthesis of DNA onto the end of chromosome during the replicative phase of cell 
cycle by telomerase may be necessary for unlimited proliferation of cells. 
Telomerase, a ribonucleoprotein enzyme is considered as a universal therapeutic 
target of cancer because of its preferential expression in cancer cells and its 
presence in 90 % of tumors. We studied the regulation of telomerase and 
telomerase reverse transcriptase catalytic subunit (TERT) by diclofenac and 
curcumin, alone and also in combination, in 1, 2-dimethylhydrazine 
dihydrochloride-induced colorectal cancer in rats. The relationship of 
telomerase activity with tumors suppressor proteins (p51, Rb, p21), cell cycle 
machinery, and apoptosis was also studied. Telomerase is highly expressed in DMH 
group and its high activity is associated with increased TERT expression. 
However, telomerase is absent or is present at lower levels in normal tissue. 
CDK4, CDK2, cyclin D1, and cyclin E are highly expressed in DMH as assessed by 
RT-PCR, qRT-PCR, Western blot, and immunofluorescence analysis. Diclofenac and 
curcumin overcome these carcinogenic effects by downregulating telomerase 
activity, diminishing the expression of TERT, CDK4, CDK2, cyclin D1, and cyclin 
E. The anticarcinogenic effects shown after the inhibition of telomerase 
activity by diclofenac and curcumin may be associated with upregulation of tumor 
suppressor proteins p51, Rb, and p21, whose activation induces the cells cycle 
arrest and apoptosis.