Prevention of Colitis-associated Cancer: Natural Compounds that Target the IL-6 Soluble Receptor

Cate      Moriasi; Dharmalingam      Subramaniam; Shanjana      Awasthi; Satish      Ramalingam; Shrikant      Anant

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.

Keywords: Chemoprevention, Chemopreventive compounds, Crohn’s disease, Chronic inflammation, Colitis-associated cancer, Colorectal cancer, Inflammatory bowel disease, Inflammatory cytokines, Interleukin-6, IL-6 signaling, IL-6 trans-signaling, Natural compounds, Soluble IL-6 receptor, STAT3, Ulcerative colitis