Targeting Inflammatory Pathways by Dietary Agents For Prevention and Therapy of Cancer

Chronic infections, obesity, alcohol, tobacco, radiation, environmental pollutants, and high-calorie diet have been recognized as major risk factors for the most common types of cancers. All these risk factors are linked to cancer through inflammation. While acute inflammation that persists for short-term mediates host defense against infections, chronic inflammation that lasts for long-term can predispose the host to various chronic illnesses, including cancer. Linkage between cancer and inflammation is indicated by numerous lines of evidence; first, transcription factors NF-kappa B and STAT3, two major pathways for inflammation, are activated by most cancer risk factors; second, an inflammatory condition precedes most cancers; third, NF-kappa B and STAT3 are constitutively active in most cancers; fourth, hypoxia and acidic conditions found in solid tumors activate NF-kappa B; fifth, chemotherapeutic agents and gamma irradiation activate NF-kappa B and lead to chemo-resistance and radio-resistance; sixth, most gene products linked to inflammation, survival, proliferation, invasion, angiogenesis, and metastasis are regulated by NT-kappa B and STAT3; seventh, suppression of NF-kappa B and STAT3 inhibits the proliferation and invasion of tumors; and eighth, most chemo-preventive agents mediate their effects through inhibition of NF-kappa B and STAT3 activation pathways. Thus suppression of these pro-inflammatory pathways may provide opportunities for both prevention and treatment of cancer. The potential of dietary agents in regulation of these inflammatory cell signaling pathways and their role in prevention and therapy of cancer, is discussed.