Role of nuclear factor κB-mediated inflammatory pathways in cancer-related symptoms and their regulation by nutritional agents

Abstract

Cancer is a disease characterized by dysregulation of multiple genes and is associated with symptoms such as cachexia, anorexia, fatigue, depression, neuropathic pain, anxiety, cognitive impairment, sleep disorders and delirium (acute confusion state) in medically ill patients. These symptoms are caused by either the cancer itself or the cancer treatment. During the past decade, increasing evidence has shown that the dysregulation of inflammatory pathways contributes to the expression of these symptoms. Cancer patients have been found to have higher levels of proinflammatory cytokines such as interleukin-6. The nuclear factor (NF)-κB is a major mediator of inflammatory pathways. Therefore, anti-inflammatory agents that can modulate the NF-κB activation and inflammatory pathways may have potential in improving cancer-related symptoms in patients. Because of their multitargeting properties, low cost, low toxicity and immediate availability, natural agents have gained considerable attention for prevention and treatment of cancer-related symptoms. How NF-κB and inflammatory pathways contribute to cancer-related symptoms is the focus of this review. We will also discuss how nutritional agents such as curcumin, genistein, resveratrol, epigallocatechin gallate and lycopene can modulate inflammatory pathways and thereby reduce cancer-related symptoms in patients.

Figures

Figure 1

Effect of cancer and cancer treatment on the patient’s life. Cancer and its treatment can cause various symptoms, which may impair the function and decrease the quality of life (A color version of this figure is available in the online journal)

Figure 2

Regulation of inflammatory cytokines through activation of nuclear factor κB (NF-κB). NF-κB is activated in response to various stimuli, including stress, diet, chemotherapeutic agents, infection and also by disease conditions such as obesity and addiction. The inflammatory molecules may induce symptoms in cancer patients. IL, interleukin; TNF-α, tumor necrosis factor α; MCP-1, monocyte chemotactic protein-1 (A color version of this figure is available in the online journal)

Figure 3

Chemical structure of nutraceuticals having the potential to modulate cancer-related symptoms. Sources of these nutraceuticals are also shown. EGCG, epigallocatechin gallate (A color version of this figure is available in the online journal)