Induction of apoptosis as a potential chemopreventive effect of dual cycloxygenase inhibitor, diclofenac, in early colon carcinogenesis.
We evaluated the role of diclofenac, a dual cycloxygenase inhibitor, in chemoprevention of 1,2-dimethylhydrazine (DMH)-induced colon carcinogenesis in rat model. In a six-week long treatment with DMH (initiation stage), colonic mucosa showed a rich presence of preneoplastic lesions, such as multiple plaque lesions (MPL), aberrant crypt foci (ACF), and histologically well-characterized dysplasia. Control animals were free from these features while simultaneous treatment of DMH and diclofenac resulted in a significant reduction of these. The Diclofenac-only group did not show any prominent carcinogenic feature. The colonic tissue showed increased COX-2 expression in the DMH group, immunohistochemically and by western blotting. Apoptosis was quantified in isolated colonocytes by fluorescent staining and by TUNEL assay in tissue sections. The number of apoptotic cells was few in the DMH group, while it was featured prominently in all the other groups. The dose of the diclofenac used in the present study was established at an anti-inflammatory dose by the carrageenan-induced rodent paw oedema test. Because ACF can be accepted as reliable prognostic biomarkers in colon carcinogenesis, its inhibition and also the induction of the apoptosis process may favorably indicate the preclinical promise for chemoprevention of colon cancer as demonstrated in the initiation phase of carcinogenesis.
Department of Biophysics, Panjab University, Chandigarh - 160 014, India.
Sankar Nath
SN
Sanyal
Jasmeet
J
Kaur
D000230:Adenocarcinoma / Q000201:enzymology / Q000473:pathology / Q000517:prevention & control*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D014408:Biomarkers, Tumor / Q000378:metabolism; D015153:Blotting, Western; D018890:Chemoprevention; D003106:Colon / Q000187:drug effects / Q000473:pathology; D003110:Colonic Neoplasms / Q000201:enzymology / Q000473:pathology / Q000517:prevention & control*; D051546:Cyclooxygenase 2 / Q000378:metabolism; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology*; D004008:Diclofenac / Q000494:pharmacology*; D004195:Disease Models, Animal; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D007413:Intestinal Mucosa / Q000187:drug effects / Q000473:pathology; D008297:Male; D011230:Precancerous Conditions / Q000201:enzymology / Q000473:pathology / Q000517:prevention & control*; D051381:Rats; D017207:Rats, Sprague-Dawley
D014408:Biomarkers, Tumor; D016861:Cyclooxygenase Inhibitors; D004008:Diclofenac; D051546:Cyclooxygenase 2; C489691:Ptgs2 protein, rat