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

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.

Omega-3 fatty acids for breast cancer prevention and survivorship

“…Other important experimental conditions include when in an animal’s lifespan supplementation is started (younger may be more protective than older), and whether agent is added to feed or administered by gavage as omega-3 fatty acids are readily oxidized once exposed to light [ 38 ]. Several preclinical studies suggest that EPA/DHA supplementation may be most optimal for prevention of estrogen receptor-positive breast cancer when used with another chemoprevention agent such as vitamin D [ 41 ], a selective estrogen receptor modulator [ 43 ], or celecoxib [ 42 ].…”

Molecular Mechanism Underling the Chemopreventive Effect of Turmeric and Banana Peel Extracts On 7, 12- Dimethylbenzeneanthracene (DMBA) - Induced Mammary Carcinogenesis in Female Mice

“…Mice treated with 20 mg/ml/week DMBA only to induce breast cancer (the dose as described by Minari and Okeke (2014) [7,8].…”

Insight in inflammation and cancer

“…Furthermore, we have recently shown that the tumor microenvironment was associated with substantial features of inflammatory marker including hypoxia and oncogenic activities (Omabe and Onyekachi, 2013) (figure 1). Another preclinical study that involved combining dosage of celecoxib (a known cox-2 inhibitor) and a dietary fats, n-3 polyunsaturated fatty acids (PUFA) often found in fish oil (which exerts cancer chemo preventive effect mediated through COX-2 inhibition); revealed that pretreatment of carcinogen-treated animals with celecoxib and/or fish oil altered inflammation mediated redox signaling with reduced c-myc, p53 expression, apoptosis, and proliferation in breast cancer model (Negi et al, 2013). However, a combination dosage of celecoxib and fish oil treatment in that study resulted in better chemo preventive effect in the female Wistar rats (Negi et al, 2013).…”

“…Another preclinical study that involved combining dosage of celecoxib (a known cox-2 inhibitor) and a dietary fats, n-3 polyunsaturated fatty acids (PUFA) often found in fish oil (which exerts cancer chemo preventive effect mediated through COX-2 inhibition); revealed that pretreatment of carcinogen-treated animals with celecoxib and/or fish oil altered inflammation mediated redox signaling with reduced c-myc, p53 expression, apoptosis, and proliferation in breast cancer model (Negi et al, 2013). However, a combination dosage of celecoxib and fish oil treatment in that study resulted in better chemo preventive effect in the female Wistar rats (Negi et al, 2013). The results suggest that a combination of celecoxib and fish oil which provide better anti-inflammatory synergy would be more effective in the chemoprevention of experimental mammary carcinogenesis, and this effect can be attributed to the modification of redox signaling.…”