Nutritional and botanical modulation of the inflammatory cascade--eicosanoids, cyclooxygenases, and lipoxygenases--as an adjunct in cancer therapy.
Emerging on the horizon in cancer therapy is an expansion of the scope of treatment beyond cytotoxic approaches to include molecular management of cancer physiopathology. The goal in these integrative approaches, which extends beyond eradicating the affected cells, is to control the cancer phenotype. One key new approach appears to be modulation of the inflammatory cascade, as research is expanding that links cancer initiation, promotion, progression, angiogenesis, and metastasis to inflammatory events. This article presents a literature review of the emerging relationship between neoplasia and inflammatory eicosanoids (PGE2 and related prostaglandins), with a focus on how inhibition of their synthesizing oxidases, particularly cyclooxygenase (COX), offers anticancer actions in vitro and in vivo. Although a majority of this research emphasizes the pharmaceutical applications of nonsteroidal anti-inflammatory drugs and selective COX-2 inhibitors, these agents fail to address alternate pathways available for the synthesis of proinflammatory eicosanoids. Evidence is presented that suggests the inhibition of lipoxygenase and its by-products-LTB4, 5-HETE, and 12-HETE-represents an overlooked but crucial component in complementary cancer therapies. Based on the hypothesis that natural agents capable of modulating both lipoxygenase and COX may advance the efficacy of cancer therapy, an overview and discussion is presented of dietary modifications and selected nutritional and botanical agents (notably, omega-3 fatty acids, antioxidants, boswellia, bromelain, curcumin, and quercetin) that favorably influence eicosanoid production.
Wallace
Jeanne M
JM
Nutritional Solutions, Inc., 2935 North, 1000 East, North Logan, UT 84341, USA. BTnutrition@aol.com
D000972:Antineoplastic Agents, Phytogenic / Q000627:therapeutic use*; D016861:Cyclooxygenase Inhibitors / Q000627:therapeutic use*; D015777:Eicosanoids / Q000502:physiology*; D006801:Humans; D007249:Inflammation / Q000503:physiopathology; D016859:Lipoxygenase Inhibitors / Q000627:therapeutic use*; D009369:Neoplasms / Q000503:physiopathology / Q000628:therapy*; D044623:Nutrition Therapy; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology
D000972:Antineoplastic Agents, Phytogenic; D016861:Cyclooxygenase Inhibitors; D015777:Eicosanoids; D016859:Lipoxygenase Inhibitors