title: Probiotic-derived ferrichrome inhibits colon cancer progression via JNK-mediated apoptosis.
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.
authors: Division of Gastroenterology and Hematology/Oncology, Department of Medicine, Asahikawa Medical University, Asahikawa 078-8510, Japan.
authors: Hiroaki
authors: H
authors: Konishi
authors: Division of Gastroenterology and Hematology/Oncology, Department of Medicine, Asahikawa Medical University, Asahikawa 078-8510, Japan.
authors: Mikihiro
authors: M
authors: Fujiya
authors: Division of Gastroenterology and Hematology/Oncology, Department of Medicine, Asahikawa Medical University, Asahikawa 078-8510, Japan.
authors: Hiroki
authors: H
authors: Tanaka
authors: Division of Gastroenterology and Hematology/Oncology, Department of Medicine, Asahikawa Medical University, Asahikawa 078-8510, Japan.
authors: Nobuhiro
authors: N
authors: Ueno
authors: Division of Gastroenterology and Hematology/Oncology, Department of Medicine, Asahikawa Medical University, Asahikawa 078-8510, Japan.
authors: Kentaro
authors: K
authors: Moriichi
authors: Division of Gastroenterology and Hematology/Oncology, Department of Medicine, Asahikawa Medical University, Asahikawa 078-8510, Japan.
authors: Junpei
authors: J
authors: Sasajima
authors: Division of Gastroenterology and Hematology/Oncology, Department of Medicine, Asahikawa Medical University, Asahikawa 078-8510, Japan.
authors: Katsuya
authors: K
authors: Ikuta
authors: Center for Advanced Research and Education, Asahikawa Medical University, Asahikawa 078-8510, Japan.
authors: Hiroaki
authors: H
authors: Akutsu
authors: Department of Gastroenterology, International University of Health and Welfare Hospital, Nasushiobara 329-2763, Japan.
authors: Hiroki
authors: H
authors: Tanabe
authors: Department of Gastroenterology, International University of Health and Welfare Hospital, Nasushiobara 329-2763, Japan.
authors: Yutaka
authors: Y
authors: Kohgo
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D002945:Cisplatin / Q000494:pharmacology; D003106:Colon / Q000166:cytology / Q000187:drug effects / Q000473:pathology; D003110:Colonic Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D018450:Disease Progression; D005291:Ferrichrome / Q000494:pharmacology* / Q000627:therapeutic use; D005472:Fluorouracil / Q000494:pharmacology; D020869:Gene Expression Profiling / Q000379:methods; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D007780:Lacticaseibacillus casei / Q000378:metabolism*; D020935:MAP Kinase Signaling System / Q000187:drug effects; D008297:Male; D013058:Mass Spectrometry; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D019936:Probiotics / Q000494:pharmacology / Q000627:therapeutic use*; D051381:Rats; D016896:Treatment Outcome; D015854:Up-Regulation
chemical_list: D000970:Antineoplastic Agents; D005291:Ferrichrome; D048031:JNK Mitogen-Activated Protein Kinases; D002945:Cisplatin; D005472:Fluorouracil