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Alteration in apoptosis and cell cycle by celecoxib and/or fish oil in 7,12-dimethyl benzene (α) anthracene-induced mammary carcinogenesis

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Tumor Biology

Abstract

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.

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Acknowledgments

The authors would like to acknowledge the University Grants Commission as Ms. Anjana Kumari Negi is the SRF-UGC. The authors thank Dr. B.N. Dutta, former Professor of Pathology and Dean of Post Graduate Institute of Medical Education and Research (PGIMER), Chandigarh, India, for his advice and expertise in immunohistochemical procedure. The authors would also like to acknowledge Mrs. Sandhya, senior technician, Central Instrumentation cell Department, PGIMER, Chandigarh, for doing flowcytometric estimations.

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  1. Department of Biochemistry, Panjab University, Chandigarh, 160014, India

    Anjana K. Negi, Shevali Kansal, Archana Bhatnagar & Navneet Agnihotri

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  1. Anjana K. Negi
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Correspondence to Navneet Agnihotri.

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Negi, A.K., Kansal, S., Bhatnagar, A. et al. Alteration in apoptosis and cell cycle by celecoxib and/or fish oil in 7,12-dimethyl benzene (α) anthracene-induced mammary carcinogenesis. Tumor Biol. 34, 3753–3764 (2013). https://doi.org/10.1007/s13277-013-0959-9

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