Inhibition of azoxymethane-induced aberrant crypt foci in rat by diphenylmethyl selenocyanate through downregulation of COX-2 and modulation of glutathione-S-transferase and lipid peroxidation.
Preventive intervention of colorectal cancer has become essential, as a major portion of the population could develop the disease at some point during their lives. An inverse association between dietary intake of selenium, an important biological trace element, and colorectal cancer risk has been observed through epidemiological and experimental studies. Inhibitory activity of an organoselenocyanate, diphenylmethylselenocyanate, was tested on azoxymethane (15 mg/kg body wt) induced colon carcinogenesis in Sprague-Dawley rats. Pretreatment and concomitant treatment, at a dose of 2 mg/kg body wt, was carried out and the effect was observed on aberrant crypt foci, the preneoplastic lesion. To investigate the mechanism of action of the compound, lipid peroxidation level and glutathione-S-transferase (GST) activities were assessed in the liver as well as in the colon. Expression of cyclooxygenase-2 protein, inducible during colon carcinogenesis, was also analyzed in the colon. Inhibitory activity of the compound was shown by the reduced incidences of aberrant crypt foci in the treated groups (by 63.3%, p=0.00044 in the pretreated group, and by 44%, p=0.0067 in the concomitant treatment group). Significant induction of GST activities and significant reduction in lipid peroxidation level both in the liver as well as in the colon and suppression of cyclooxygenase-2 expression in the colon of the treated groups suggest that the compound could exert its preventive effect at different levels of the carcinogenic process. The preventive effect was better in the pretreatment group than in the concomitant treatment group, suggesting some added protection to the target tissue resulting from preadministration of the compound.
Ghosh
Samit
S
Department of Cancer Chemoprevention, Chittaranajan National Cancer Institute, 37, S.P. Mukherjee Road, Kolkata-700026, India.
Das
Rajat Kumar
RK
Sengupta
Archana
A
Bhattacharya
Sudin
S
D000818:Animals; D001397:Azoxymethane / Q000633:toxicity*; D015153:Blotting, Western; D003106:Colon / Q000201:enzymology / Q000378:metabolism; D015179:Colorectal Neoplasms / Q000517:prevention & control; D051546:Cyclooxygenase 2; D015536:Down-Regulation; D004591:Electrophoresis, Polyacrylamide Gel; D005982:Glutathione Transferase / Q000096:biosynthesis* / Q000378:metabolism; D015227:Lipid Peroxidation; D008099:Liver / Q000201:enzymology; D008297:Male; D008956:Models, Chemical; D009374:Neoplasms, Experimental / Q000139:chemically induced / Q000188:drug therapy; D016566:Organoselenium Compounds / Q000494:pharmacology*; D011451:Prostaglandin-Endoperoxide Synthases / Q000096:biosynthesis*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012643:Selenium / Q000494:pharmacology*; D013997:Time Factors
D016566:Organoselenium Compounds; C495419:diphenylmethyl selenocyanate; D051546:Cyclooxygenase 2; D011451:Prostaglandin-Endoperoxide Synthases; D005982:Glutathione Transferase; D012643:Selenium; D001397:Azoxymethane