Abstract
Calorie restriction (CR) is one of the most potent broadly acting dietary interventions for inducing weight loss and for inhibiting cancer in experimental models. Translation of the mechanistic lessons learned from research on CR to cancer prevention strategies in human beings is important given the high prevalence of excess energy intake, obesity, and metabolic syndrome in many parts of the world and the established links between obesity-associated metabolic perturbations and increased risk or progression of many types of cancer. This review synthesizes findings on the biological mechanisms underlying many of the anticancer effects of CR, with emphasis on the impact of CR on growth factor signaling pathways, inflammation, cellular and systemic energy homeostasis pathways, vascular perturbations, and the tumor microenvironment. These CR-responsive pathways and processes represent targets for translating CR research into effective cancer prevention strategies in human beings.
Highlights
Calorie restriction (CR), a dietary regimen in which subjects receive a reduced energy diet, is one of the most potent and broadly acting dietary interventions for preventing or reversing weight gain and inhibiting cancer in experimental tumor models [1]
Recent reports of decreased risk of diabetes, neurological degeneration, and cancer in response to CR in rhesus monkeys [2,3], and observations that CR decreases inflammatory and endocrine markers associated with increased breast cancer risk in women [4,5], suggest that the beneficial effects of CR on metabolism and chronic disease risk observed in rodent models may extend to human beings
These findings are consistent with recent studies in women at high risk for breast cancer showing that inflammatory and growth factor signaling pathways are reduced by total CR or 2 days/week of restricted carbohydrate calories [4,5]
Summary
Calorie restriction (CR), a dietary regimen in which subjects (typically test animals) receive a reduced energy diet (typically, a 20 to 40% reduction in total energy intake relative to an unrestricted comparison group), is one of the most potent and broadly acting dietary interventions for preventing or reversing weight gain and inhibiting cancer in experimental tumor models [1]. Preliminary reports on CALERIE indicate that many of the same metabolic and endocrine changes observed in rodents and monkeys are occurring in human beings in response to CR [13,14] These findings are consistent with recent studies in women at high risk for breast cancer showing that inflammatory and growth factor signaling pathways are reduced by total CR or 2 days/week of restricted carbohydrate calories [4,5]. CR promotes a mesenchymal-to-epithelial transition in the mammary gland by increasing the expression of the epithelial markers, such as E-cadherin, and decreasing the expression of mesenchymal markers, such as N-cadherin and fibronectin [115] Taken together, these studies suggest an important role for the microenvironment in the response of stem cells (including cancer stem cells) to CR or CR mimetics targeting the mTOR pathway, and this will no doubt be an important and exciting research area in the coming years. Future studies aimed at further elucidating the mechanisms underlying the anticancer effects of CR, and that exploit this mechanistic information to target CR-responsive pathways will facilitate the translation of CR research into effective cancer prevention strategies in human beings
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