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Helminth‐derived molecules inhibit colitis‐associated colon cancer development through NF‐κB and STAT3 regulation
Author(s) -
Callejas Blanca E.,
MendozaRodríguez Mónica G.,
VillamarCruz Olga,
ReyesMartínez Sandy,
SánchezBarrera Cuauhtémoc Angel,
RodríguezSosa Miriam,
DelgadoBuenrostro Norma L.,
MartínezSaucedo Diana,
Chirino Yolanda I.,
LeónCabrera Sonia A.,
PérezPlasencia Carlos,
VacaPaniagua Felipe,
AriasRomero Luis E.,
Terrazas Luis I.
Publication year - 2019
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.32626
Subject(s) - colitis , nf κb , colorectal cancer , stat3 , helminths , cancer research , cancer , biology , medicine , immunology , signal transduction , inflammation , microbiology and biotechnology
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‐chain‐enhancer 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 three‐dimensional 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 helminth‐derived molecules on suppressing ongoing colorectal cancer by downregulating proinflammatory and protumorigenic signaling pathways.