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.

The Potential Role of Curcumin for Treatment of Pancreatic Cancer

“…fatigue, pain, constipation). We cannot rule out the placebo effect; however, several preclinical studies demonstrating that curcumin can improve fatigue, depression or neuropathic pain support our current observation (Gupta et al, 2011;Sharma et al, 2006;Xu et al, 2005). Therefore, curcumin could improve the quality of life of patients with pancreatic cancer by alleviating cancer-related symptoms, and this could indirectly contribute to the improved overall survival.…”

Bortezomib Inhibits Giant Cell Tumor of Bone through Induction of Cell Apoptosis and Inhibition of Osteoclast Recruitment, Giant Cell Formation, and Bone Resorption

“…Numerous NF-kB-regulated genes are involved in cancer cell survival, proliferation, invasion, angiogenesis, metastasis, and cytokine secretion (36). Therefore, the NF-kB signaling pathway has become an attractive potential target for drug discovery (37). A wide variety of agents, including inhibitors of protein kinases, protein phosphatases, proteasomes, ubiquitination, acetylation, methylation, and the DNA-binding steps of NF-kB signaling pathway, have been identified as potential NF-kB-targeting agents (36).…”

Key cell signaling pathways modulated by zerumbone: Role in the prevention and treatment of cancer

“…Others act as cancer suppressing agents, and can inhibit the development of cancerinitiated cells to pre-neoplastic and neoplastic cells [22,23]. However, in most cases, a given phytochemical can execute a multitude of intracellular effects, rather than a specific biological interaction, and the combination of these effects eventually facilitates cancer prevention/treatment [24,25]. Many phytochemicals are also found to modulate inflammation-related molecular targets [26,27].…”