Table 5.
n-3 PUFA and breast cancer risk: Chemically-induced rodent models.
| Carcinogen | n-3 PUFA Source | Feeding Period | Main Findings | Mechanism | Reference |
|---|---|---|---|---|---|
| MNU | Fish oil 2%–10% w/w n-3 PUFA in diet | 18-week (at the same time as MNU administration) | Absolute n-3 diet: ↓ body weight, no tumor occurrence (10% w/w n-3 PUFA) 1:1n-6/n-3 diet ↓ tumor incidence and multiplicity (5% w/w n-3 PUFA) | ↑ EPA, DHA in mammary ↓ FAS, COX-2, 5-LOX | [64] |
| MNU | Fish oil concentrate Low n-6/n-3 = 1:14.6 High n-6/n-3 = 1:0.7 | 2-week (at the same time as MNU administration) | Low vs. high ratio n-6/n-3 PUFA diet: ↓ tumor incidence (21%), ↓ tumor multiplicity (30%), tumor burden (80%) ↑ apoptotic index (129%) | ↓ Ki-67 ↑ Bax, Bax/Bcl2, PPARγ ↓ NF-κB p65, pAkt, IGF-IR | [87] |
| MNU | EPA/DHA alone: 95 g/kg EPA/DHA EPA + DHA: 47.5 g/kg EPA + 47.5 g/kg DHA | 20-week (at the same time as MNU administration) | DHA alone vs EPA + DHA vs EPA alone: ↓ tumor incidence: 23%, 73%, 65% ↓ tumor multiplicity: 0.23, 1.67, 1.59 DHA is more effectively than EPA | NA | [120] |
| DMBA | Maxepa (fish oil concentrate): 90 mg EPA + 60 mg DHA per day | 24-week study 35-week study (before DMBA injection) | ↓ DNA single-strand breaks ↓ cell proliferation | ↓ Ki-67, Her-2/neu | [26] |
| DMBA | Maxepa: 90 mg EPA + 60 mg DHA per day | 24-week study 35-week study (before DMBA injection) | ↓ tumor incidence (23%), tumor multiplicity (42%) ↑ cell apoptosis ↓cell proliferation | ↓ Bcl-2 ↑Bax ↑ p53 | [27,28] |
| DMBA | Fish oil (0.5%ALA, 16% EPA, 1.2% DPA, 8% DHA in fish oil) | NA | ↓ tumor incidence with fish oil consumption: adulthood < in utero < puberty < perinatal ↓ tumor multiplicity with fish oil consumption: adulthood > puberty > perinatal > in utero | ↓ maternal serum estradiol | [29] |
| DMBA | Menhaden oil Low-fat n-3 PUFA diet: 4.6 g/kg EPA + 3.2 g/kg DHA High fat n-3 PUFA diet: 9.1 g/kg EPA + 6.3 g/kg DHA | 20-day (before DMBA injection) | Low n-3 diet: ↓ tumor incidence ↓ TEBs ↓ cell proliferation ↑ cell apoptosis; High n-3 diets exert opposite effects | Low n-3 diet: ↓ COX-2, PCNA ↑ PPARγ ↑ lipid peroxidation High n-3 diet: ↑ pAkt ↑ lipid peroxidation | [110] |
↑: increase; ↓: decrease; NA: not available.