Helminth‐derived molecules inhibit colitis‐associated colon cancer development through NF‐κB and STAT3 regulation

Abstract

Inflammation is currently considered a hallmark of cancer and plays a decisive role in different stages of tumorigenesis, including initiation, promotion, progression, metastasis and resistance to antitumor therapies. Colorectal cancer is a disease widely associated with local chronic inflammation. Additionally, extrinsic factors such as infection may beneficially or detrimentally alter cancer progression. Several reports have noted the ability of various parasitic infections to modulate cancer development, favoring tumor progression in many cases and inhibiting tumorigenesis in others. The aim of our study was to determine the effects of excreted/secreted products of the helminth Taenia crassiceps (TcES) as a treatment in a murine model of colitis-associated colon cancer (CAC). Here, we found that after inducing CAC, treatment with TcES was able to reduce inflammatory cytokines such as IL-1β, TNF-α, IL-33 and IL-17 and significantly attenuate colon tumorigenesis. This effect was associated with the inhibition of signal transducer and activator of transcription 3 and nuclear factor kappa-light-chainenhancer of activated B cells (NF-κB) phosphorylation. Furthermore, we determined that TcES interfered with LPS-induced NF-κB p65 activation in human colonic epithelial cell lines in a Raf-1 proto-oncogene-dependent manner. Moreover, in threedimensional cultures, TcES promoted reorganization of the actin cytoskeleton, altering cell morphology and forming colonospheres, features associated with a low grade of aggressiveness. Our study demonstrates a remarkable effect of Additional Supporting Information may be found in the online version of this article.

Exopolysaccharides isolated from Rhizopus nigricans induced colon cancer cell apoptosis in vitro and in vivo via activating the AMPK pathway

“…Therefore, there is an urgent need to explore novel substances as therapeutic agents against CRC with few or no adverse side effects. Fortunately, several studies have shown that naturally active polysaccharides, extracted from fungi, plants, animals, algae, and lichens [3][4][5][6], possess anti-CRC properties [7,8] through a variety of mechanisms.…”

The Antitumor Efficacy of β-Elemene by Changing Tumor Inflammatory Environment and Tumor Microenvironment

“…Tumor-Promoting Pathways. The transcription factors NF-κB and STAT3 are involved in inflammation and tumorigenesis and regulate cell survival, growth, and proliferation [97]. Many cytokines involved in the inflammatory response, such as TNF and IL-1, are involved in the activation of the NF-κB signaling pathway [88].…”

“…In the Th1 cell-mediated EAE animal model, β-elemene improves the course of EAE mice by inhibiting RORγt, which is activated by the IL-6 and STAT3 pathways [129]. The NF-κB and STAT3 pathways play key roles in the formation of the inflammatory environment, as well as in the development, invasion, and metastasis of tumors [97]. The inhibitory effect of β-elemene on these two pathways has shown good antiinflammatory and anticancer applications, but this requires further research.…”

Use of STAT6 Phosphorylation Inhibitor and Trimethylglycine as New Adjuvant Therapies for 5-Fluorouracil in Colitis-Associated Tumorigenesis

“…For immunohistochemical analysis, the sections were deparaffinized in xylene and then rehydrated with graded alcohols and processed as reported previously [69]. The sections were incubated overnight at 4 • C with the respective primary antibodies diluted in 1× PBS (anti-E-cadherin, 1:300, cell signaling; anti-β-catenin, 1:200, GeneTex, Irvine, CA, USA) and then developed following the conventional technique.…”