Probiotic-derived ferrichrome inhibits colon cancer progression via JNK-mediated apoptosis

Hiroaki Konishi, Mikihiro Fujiya (), Hiroki Tanaka, Nobuhiro Ueno, Kentaro Moriichi, Junpei Sasajima, Katsuya Ikuta, Hiroaki Akutsu, Hiroki Tanabe and Yutaka Kohgo
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Hiroaki Konishi: Asahikawa Medical University
Mikihiro Fujiya: Asahikawa Medical University
Hiroki Tanaka: Asahikawa Medical University
Nobuhiro Ueno: Asahikawa Medical University
Kentaro Moriichi: Asahikawa Medical University
Junpei Sasajima: Asahikawa Medical University
Katsuya Ikuta: Asahikawa Medical University
Hiroaki Akutsu: Center for Advanced Research and Education, Asahikawa Medical University
Hiroki Tanabe: International University of Health and Welfare Hospital
Yutaka Kohgo: International University of Health and Welfare Hospital

Nature Communications, 2016, vol. 7, issue 1, 1-12

Abstract: Abstract Previous reports have suggested that some probiotics inhibit tumorigenesis and cancer progression. However, the molecules involved have not yet been identified. Here, we show that the culture supernatant of Lactobacillus casei ATCC334 has a strong tumour-suppressive effect on colon cancer cells. Using mass spectrometry, we identify ferrichrome as a tumour-suppressive molecule produced by L. casei ATCC334. The tumour-suppressive effect of ferrichrome is greater than that of cisplatin and 5-fluorouracil, and ferrichrome has less of an effect on non-cancerous intestinal cells than either of those agents. A transcriptome analysis reveals that ferrichrome treatment induces apoptosis, which is mediated by the activation of c-jun N-terminal kinase (JNK). Western blotting indicates that the induction of apoptosis by ferrichrome is reduced by the inhibition of the JNK signalling pathway. This we demonstrate that probiotic-derived ferrichrome exerts a tumour-suppressive effect via the JNK signalling pathway.

Date: 2016
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DOI: 10.1038/ncomms12365

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