Calorie restriction and cancer prevention: a mechanistic perspective

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.

Figure 1

Calorie restriction and cancer: overview of mechanisms. Chronic exposure to a calorie restriction regimen results in reduced circulating levels of several hormones, growth factors and cytokines, leading to decreased growth factor signaling, fewer vascular perturbations, and decreased inflammation. Together, these responses to calorie restriction result in decreased cancer risk and progression. An arrow preceding text denotes a directional effect (eg, activity or concentration). Abbreviations: IGF-1, insulin-like growth factor-1; ApN, adiponectin; PAI–1, plasminogen activator inhibitor–1; tPA, tissue-type plasminogen activator; uPA, urokinase-type plasminogen activator; VEGF, vascular endothelial growth factor; PI3K, phosphoinositide 3-kinase; mTOR, mammalian targt of rapamycin; NF-kB, nuclear factor kB; COX-2, cyclooxygenase-2.