Alteration in apoptosis and cell cycle by celecoxib and/or fish oil in 7,12-dimethyl benzene (α) anthracene-induced mammary carcinogenesis.
Cyclooxygenase (COX)-2 inhibition by nonsteroidal anti-inflammatory drugs is a useful approach for cancer prevention but has several side effects. A novel approach combining these chemopreventive agents at low doses with dietary elements has been suggested to augment their effects and reduce side effects. Dietary fats, particularly, n-3 polyunsaturated fatty acids (PUFA) also exert cancer chemopreventive effect mediated through COX-2 inhibition. Therefore, the present study was designed to investigate the effect of combined dosage of celecoxib and n-3 PUFA-rich fish oil in experimental mammary carcinogenesis. Female Wistar rats were distributed into control and DMBA-treated groups. The groups were further subdivided based on pretreatment with celecoxib and/or fish oil. The animals were maintained for 90 days before sacrifice. To analyze the role of redox signaling, the two mediators, reactive oxygen species and calcium, and their effects on c-myc expression were evaluated. The chemopreventive effect was assessed by measurement of cell proliferation, apoptosis, and p53 in isolated mammary epithelial cells. Increased redox signaling with enhanced c-myc, p53 expression, and augmented apoptotic and proliferative rate were observed in carcinogen-treated animals. Pretreatment of carcinogen-treated animals with celecoxib and/or fish oil altered redox signaling with reduced c-myc, p53 expression, apoptosis, and proliferation. However, a combination dosage of celecoxib and fish oil had a better chemopreventive effect. The results suggest that a combination of celecoxib and fish oil is more effective in the chemoprevention of experimental mammary carcinogenesis, and this effect can be attributed to the modification of redox signaling.
Department of Biochemistry, Panjab University, Chandigarh, 160014, India.
Anjana K
AK
Negi
Shevali
S
Kansal
Archana
A
Bhatnagar
Navneet
N
Agnihotri
D015127:9,10-Dimethyl-1,2-benzanthracene; D000818:Animals; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D002118:Calcium / Q000378:metabolism; D000068579:Celecoxib; D002453:Cell Cycle / Q000187:drug effects*; D002478:Cells, Cultured; D052246:Cyclooxygenase 2 Inhibitors / Q000008:administration & dosage / Q000494:pharmacology; D004847:Epithelial Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D015525:Fatty Acids, Omega-3 / Q000008:administration & dosage / Q000494:pharmacology; D005260:Female; D005395:Fish Oils / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology*; D005434:Flow Cytometry; D007150:Immunohistochemistry; D053539:Keratin-19 / Q000378:metabolism; D008321:Mammary Glands, Animal / Q000166:cytology; D008325:Mammary Neoplasms, Experimental / Q000139:chemically induced / Q000378:metabolism / Q000517:prevention & control*; D016271:Proto-Oncogene Proteins c-myc / Q000378:metabolism; D011720:Pyrazoles / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D017382:Reactive Oxygen Species / Q000378:metabolism; D013449:Sulfonamides / Q000008:administration & dosage / Q000494:pharmacology*; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
D052246:Cyclooxygenase 2 Inhibitors; D015525:Fatty Acids, Omega-3; D005395:Fish Oils; D053539:Keratin-19; C489428:Myc protein, mouse; D016271:Proto-Oncogene Proteins c-myc; D011720:Pyrazoles; D017382:Reactive Oxygen Species; D013449:Sulfonamides; D016159:Tumor Suppressor Protein p53; D015127:9,10-Dimethyl-1,2-benzanthracene; D000068579:Celecoxib; D002118:Calcium