title: Prevention of colitis-associated cancer: natural compounds that target the IL-6 soluble receptor.
abstract: The risk of developing colorectal cancer increases in patients with inflammatory bowel disease (IBD) and a growing body of evidence shows the critical role of interleukin (IL-6) in this process. IL-6 is both a pro- and anti-inflammatory cytokine whose effects are mediated through activation of STAT3. Recent studies have also demonstrated that IL-6 trans-signaling through its soluble receptor occurs in IBD and cancer. IL-6 trans-signaling therefore is emerging as an attractive approach to diminish the inflammatory signals in conditions of chronic inflammation. The purpose of cancer chemoprevention is to either delay the onset or progression from precancerous lesions. Natural compounds because of their low toxicity render themselves excellent candidates that can be administered over the lifetime of an individual. With the focus of managing IBD over a long time and preventing onset of colitis-associated cancer, we believe that there should be increased research focus on identifying chemopreventive compounds that can render themselves to long term use possibly for the lifetime of predisposed individuals. Here, we review the role of IL-6 signaling in IBD and colitis-associated cancer and underscore the importance of searching for natural compounds that would target the IL-6 trans-signaling pathway as a way to diminish chronic inflammatory conditions in the gastrointestinal tract and possibly hamper the progression to colon cancer. We propose that effective screening and identification of natural chemopreventive compounds that target IL-6 trans-signaling has important implications for the development of optimal strategies against cancer development triggered by inflammation.
authors.affiliation: Department of Molecular and Integrative Physiology, University of Kansas Medical Center, Kansas City, KS 66160, USA.
authors.forename: Cate
authors.initials: C
authors.lastname: Moriasi
authors.forename: Dharmalingam
authors.initials: D
authors.lastname: Subramaniam
authors.forename: Shanjana
authors.initials: S
authors.lastname: Awasthi
authors.forename: Satish
authors.initials: S
authors.lastname: Ramalingam
authors.forename: Shrikant
authors.initials: S
authors.lastname: Anant
mesh_terms: D000818:Animals; D001688:Biological Products / Q000302:isolation & purification / Q000494:pharmacology / Q000627:therapeutic use*; D003092:Colitis / Q000150:complications* / Q000188:drug therapy / Q000276:immunology; D003110:Colonic Neoplasms / Q000209:etiology / Q000276:immunology / Q000517:prevention & control*; D006801:Humans; D007413:Intestinal Mucosa / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D016032:Randomized Controlled Trials as Topic; D019947:Receptors, Interleukin-6 / Q000037:antagonists & inhibitors*; D015398:Signal Transduction / Q000187:drug effects; D012995:Solubility; D016896:Treatment Outcome
chemical_list: D001688:Biological Products; D019947:Receptors, Interleukin-6