Title:Prevention of Colitis-associated Cancer: Natural Compounds that Target the IL-6 Soluble Receptor
Volume: 12
Issue: 10
Author(s): Cate Moriasi, Dharmalingam Subramaniam, Shanjana Awasthi, Satish Ramalingam and Shrikant Anant
Affiliation:
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
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.
