Ferrichrome identified from Lactobacillus casei ATCC334 induces apoptosis through its iron-binding site in gastric cancer cells
Ferrichrome identified from Lactobacillus casei ATCC334 induces apoptosis through its iron-binding site in gastric cancer cells
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DOI：
10.1177/1010428317711311
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发表时间：
2017-06-22
期刊：
影响因子：
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通讯作者：
Okumura, Toshikatsu
中科院分区：
文献类型：
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作者：
Ijiri, Masami;Fujiya, Mikihiro;Okumura, Toshikatsu
铁色素是已知的铁载体，但它最近被鉴定为来自干酪乳杆菌ATCC 334（L. casei）。在本研究中，我们研究了铁色素在胃癌细胞中的作用。用铁色素处理的细胞系和异种移植模型表现出生长抑制。裂解的聚（腺苷二磷酸-核糖）聚合酶的表达水平，和裂解的半胱天冬酶-9的铁染色处理增加。虽然铁色素的肿瘤抑制作用几乎完全减弱的铁螯合，铁色素的细胞内铁的减少并不与其肿瘤抑制作用。一个详尽的对接模拟表明，无铁的铁色素可以与各种哺乳动物分子，包括转运蛋白和受体的稳定构象。总之，益生菌来源的铁色素诱导胃癌细胞凋亡。铁色素的铁结合位点是负责其肿瘤抑制功能的结构。
Ferrichrome is known to be a siderophore, but it was recently identified as a tumor-suppressive molecule derived from Lactobacillus casei ATCC334 (L. casei). In the present study, we investigated the effects of ferrichrome in gastric cancer cells. Cell lines and xenograft models treated with ferrichrome demonstrated growth suppression. The expression levels of cleaved poly (adenosine diphosphate-ribose) polymerase, and cleaved caspase-9 were increased by ferrichrome treatment. Although the tumor-suppressive effects of ferrichrome were almost completely diminished by the iron chelation, the reduction in the intracellular iron by ferrichrome did not correlate with its tumor-suppressive effects. An exhaustive docking simulation indicated that iron-free ferrichrome can make stable conformations with various mammalian molecules, including transporters and receptors. In conclusion, probiotic-derived ferrichrome induced apoptosis in gastric cancer cells. The iron binding site of ferrichrome is the structure responsible for its tumor suppressive function.