乳酸菌由来フェリクロームは大腸癌細胞に対して小胞体ストレス経路を活性化して抗腫瘍効果を発揮する

抄録

Previous investigations revealed that some probiotic bacteria exert anti-tumor effects in colorectal cancer. However, the anti-tumor molecules produced by probiotic bacteria have been less identified. In this study, we showed the strong anti-tumor effect of culture supernatant of Lactobacillus spices, and therefore identified ferrichrome as a tumor-suppressing molecule from the culture supernatant of L. casei using the HPLC separation system and mass spectrometry analysis. Anti-tumor effect of ferrichrome was superior than classical anti-tumor agents, including cisplatin and 5-FU. Ferrichrome induced the apoptotic reactions, including DNA fragmentation and cleavage of caspase-3 and PARP, in colorectal cancer cells. Transcriptome analysis revealed that ferrichrome induced DDIT3-mediated endoplasmic stress pathway. Ferrichrome exhibited an antitumor effect in a xenograft model, an AOM-DSS-induced carcinogenesis model and patient-derived organoid model. The biochemical test values were not markedly different when ferrichrome was administrated to mice. Therefore, we demonstrated that ferrichrome derived from L. casei suppressed the progression of colorectal cancer cell with little adverse effect, suggesting that it may be a novel agent for treating colorectal cancer.