Role of oxidative stress in the preventive effects of calorie restriction for breast cancer development in MMTV-TGF-α mice

Breast cancer is one of the main causes of deaths among women worldwide. Despite of countless studies on breast cancer, there are still limited numbers of successful treatments and efficient prevention strategies for it until today. On the other hand, calorie restriction (CR) is one of the most effective methods to prevent several diseases including cancer. However, the molecular mechanism of which remains unclear. The aim of this study was to understand the role of oxidative stress in the preventive effects of CR against breast cancer development in MMTV-TGF-α transgenic mouse model. Mice at 10 weeks of ages were enrolled in ad libitum (AL), Chronic Calorie Restriction (CCR, 15 per cent CR application) or Intermittent Calorie Restriction (ICR, three weeks of AL feeding and one week 60 per cent CR application in cyclic periods) groups. Blood and liver samples were collected from each dietary groups to measure malondialdehyde (MDA), glutathione (GSH) levels and catalase (CAT), glutathione peroxidase (GSH-Px) and superoxide dismutase (SOD) activity at 10, 17/18, 49/50 and 81/82 weeks of ages. Decreased body weight and lower mammary tumor (MT) incidence were observed in CCR group in the current study. In accordance with body weight and MT incidence data, CCR group had lower erythrocytes MDA level (p>0.05) at 17/18 and 49/50 weeks of ages. Moreover, ICR-R group had higher MDA level compared to CCR and AL at 81/82 weeks of ages. In addition, CCR group maintained its MDA level due to aging while ICR groups had gradually increasing MDA level due to aging (p<0.05). Moreover, CCR group had higher erythrocytes CAT and SOD activity compared to ICR and AL groups. CAT and SOD activity was also found to be positively correlated in erythrocytes samples throughout the study (p<0.05). Erythrocytes GSH level was higher in CCR group compared to ICR groups at week 49/50 (p<0.05) while there was no significant effect of different types of CR on GSH-PX activity. In the present study, the long term (82 weeks) effects and direct comparison of different types of CR on oxidative stress parameters in erythrocytes and liver samples were reported for the first time. In conclusion, CCR types of calorie restriction has better protective roles against oxidative stress than ICR types of CR.