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J Cancer Metastasis Treat 2020;6:5 I http://dx.doi.org/10.20517/2394-4722.2020.13 Page 35 of 38

48. The microbiota-derived metabolite butyrate inhibits colorectal cancer cell migration via
modulation of autophagy

Eleonora Secomandi, Chiara Vidoni, Alessandra Ferraresi, Giulia Camurani, Ciro Isidoro

Laboratory of Molecular Pathology and Nanobioimaging, Department of Health Sciences, Università del
Piemonte Orientale, Via Solaroli 17, Novara 28100, Italy.

Background: Colorectal cancer (CRC) is the third most common cause of cancer deaths worldwide. The
etiology of CRC involves host genetic predisposition and environmental factors, among which the diet
plays an important role. The proportion of dietary fiber and meat consumed influences the composition
[1]
of intestinal microbiota, which get energy from ingested food . One of the main metabolites produced by
gut microbiota is the short chain fatty acid butyrate. Butyrate exerts a beneficial role in the maintenance of
[1]
intestinal epithelium integrity through various mechanisms . Autophagy is the main cellular process that
[2]
promotes a balanced macromolecular turnover and guarantees cell homeostasis .
Aim: We studied the anti-migratory and anti-inflammatory properties of butyrate, a probiotic metabolite, in
a colorectal cancer cellular model. Furthermore, we investigated the molecular pathways underlying these
effects, with a particular focus on autophagy.

Experimental procedure: HCT116 colorectal cancer cells were treated with 5-mM sodium butyrate and
50-ng/mL interleukin-6 (IL-6). To study cell motility, a wound healing scratch assay was performed.
Cellular homogenates were employed for protein expression studies through Western blot analysis.
Immunofluorescence was performed on fixed cells.

Results: We found that butyrate counteracts colorectal cancer cell migration, even in the presence of IL-6, a
well known pro-inflammatory cytokine. This effect is accompanied with a reduced expression of activated
STAT3 and Twist1. Furthermore, the probiotic metabolite prevents IL-6-induced expression of N-cadherin,
a typical hallmark of epithelial-to-mesenchymal transition. In addition, butyrate strongly accelerates
the autophagy flux, alone and in co-presence with IL-6, suggesting autophagy as a putative mechanism
responsible for slowing down cell motility.

Conclusion: Taken together, our findings identified anti-cancer properties of butyrate, in particular its ability
to counteract IL-6-induced colon cancer cell migration, by upregulating autophagy.

REFERENCES
1. Wu X, Wu Y, He L, Wu L, Wang X, et al. Effects of the intestinal microbial metabolite butyrate on the development of colorectal cancer. J
Cancer 2018;9:2510-7.
2. Mizushima N, Levine B. Autophagy in mammalian development and differentiation. Nat Cell Biol 2010;12:823-30.

49. Parasites and cancer

Omar M. Amin

Parasitology Center Inc, Scottsdale, AZ 85259, USA.

This PowerPoint presentation is based on our work at Parasitology Center, Inc. (PCI), in Scottsdale,
Arizona, USA and covers the diagnosis, pathology, relationships with cancer, and treatment of human