Probiotic-derived ferrichrome inhibits colon cancer progression via JNK-mediated apoptosis.
Probiotic-derived ferrichrome inhibits colon cancer progression via JNK-mediated apoptosis.
复制标题
益生菌衍生的铁晶体通过JNK介导的凋亡抑制结肠癌的进展。
DOI：
10.1038/ncomms12365
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发表时间：
2016-08-10
影响因子：
16.6
通讯作者：
Kohgo Y
中科院分区：
文献类型：
--
作者：
Konishi H;Fujiya M;Tanaka H;Ueno N;Moriichi K;Sasajima J;Ikuta K;Akutsu H;Tanabe H;Kohgo Y
以前的报告表明，一些益生菌可以抑制肿瘤的发生和癌症的进展。然而，所涉及的分子尚未被确定。本研究表明，干酪乳杆菌ATCC334培养上清液对结肠癌细胞具有很强的抑瘤作用。通过质谱分析，我们鉴定出铁铬是一种由干酪乳杆菌ATCC334产生的肿瘤抑制分子。铁铬的肿瘤抑制作用大于顺铂和5-氟尿嘧啶，而铁铬对非癌性肠细胞的作用小于这两种药物。转录组分析显示，铁铬处理诱导细胞凋亡，这是通过激活c-jun n -末端激酶（JNK）介导的。Western blotting表明，铁铬对细胞凋亡的诱导作用因JNK信号通路的抑制而减弱。本研究表明，益生菌衍生的铁铬通过JNK信号通路发挥肿瘤抑制作用。益生菌在肿瘤细胞系和动物模型中具有肿瘤抑制作用。在本研究中，作者证明了干酪乳杆菌ATCC334产生的铁铬可以通过JNK途径抑制结肠癌生长诱导凋亡。
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. Probiotics have tumour-suppressive effects in cancer cell lines and in animal models. In this study, the authors demonstrate that ferrichrome produced by Lactobacillus casei ATCC334 can suppress colon cancer growth inducing apoptosis via the JNK pathway.