Bacteria-derived ferrichrome inhibits tumor progression in sporadic colorectal neoplasms and colitis-associated cancer.
Bacteria-derived ferrichrome inhibits tumor progression in sporadic colorectal neoplasms and colitis-associated cancer.
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DOI：
10.1186/s12935-020-01723-9
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发表时间：
2021-01-06
影响因子：
5.8
通讯作者：
Okumura T
中科院分区：
文献类型：
--
作者：
Iwama T;Fujiya M;Konishi H;Tanaka H;Murakami Y;Kunogi T;Sasaki T;Takahashi K;Ando K;Ueno N;Kashima S;Moriichi K;Tanabe H;Okumura T
结直肠癌通过几种途径发展，包括腺瘤-癌序列和结肠炎相关的癌变。据报道，肠道菌群的改变与结直肠癌的发生和发展有关，通过这些途径。我们通过上调DDIT3，确定干酪乳杆菌来源的铁色素是结直肠癌细胞的细菌抗肿瘤效应的介体。在这项研究中，我们研究了铁铬对癌前状态和与散发性和结肠炎相关的结直肠癌相关的癌细胞的抗肿瘤作用。采用SRB法和四甲基偶氮唑盐比色法检测细胞生长抑制情况。从结肠镜活检标本中制备了18种有机化合物。建立AOM-DSS结直肠癌细胞致癌模型和结直肠癌细胞异种移植模型，以评价铁铬在体内的抑瘤作用。铁铬在体外和体内异种移植模型中均能抑制结直肠癌细胞的生长。无论是在体内还是体外，铁罗明都表现出了比目前可用的抗肿瘤药物5-FU和顺铂更强的抑瘤作用。铁铬联合5-FU的抑瘤效果优于单独用药。通过患者来源的腺瘤和癌组织中DDIT3的上调，证实了铁铬的肿瘤抑制作用。在AOM-DSS模型中，铁色素抑制肿瘤进展，而在DSS-结肠炎模型中没有显示出抗炎作用，这表明铁色素通过结肠炎相关途径抑制癌细胞，但不是癌前状态。Ferichrome对癌前疾病和与散发性和结肠炎相关的结直肠癌相关的癌细胞具有肿瘤抑制作用。铁试剂的抗肿瘤作用是通过上调DDIT3实现的，且优于5-FU或顺铂。这些结果表明，短链乳杆菌铁色素可能是一种治疗结直肠癌的候选抗肿瘤药物。
Colorectal cancers develop through several pathways, including the adenoma–carcinoma sequence and colitis-associated carcinogenesis. An altered intestinal microflora has been reported to be associated with the development and progression of colorectal cancer via these pathways. We identified Lactobacillus casei-derived ferrichrome as a mediator of the bacterial anti-tumor effect of colorectal cancer cells through the upregulation of DDIT3. In this study, we investigated the anti-tumor effects of ferrichrome on precancerous conditions and cancer cells associated with sporadic as well as colitis-associated colorectal cancer. SRB and MTT assays were performed to assess growth inhibition in vitro. Eighteen organoids were prepared from biopsy specimens obtained by colonoscopy. An AOM-DSS carcinogenesis model and xenograft model of colorectal cancer cells were generated for the assessment of the tumor suppressive effect of ferrichrome in vivo. Ferrichrome inhibited the cell growth of colorectal cancer cells in vitro and in in vivo xenograft models. Ferrichrome exerted a strong tumor-suppressive effect that was superior to that of currently available anti-tumor agents, including 5-FU and cisplatin, both in vitro and in vivo. The tumor-suppressive effect of the combination of ferrichrome and 5-FU was superior to that of single treatment with either drug. The tumor suppressive effects of ferrichrome were confirmed through the upregulation of DDIT3 in patient-derived organoids of adenoma and carcinoma. Ferrichrome inhibited the tumor progression in the AOM-DSS model while exhibiting no anti-inflammatory effect in the DSS-colitis model, suggesting that ferrichrome inhibited cancer cells, but not a precancerous condition, via the colitis-associated pathway. Ferrichrome exerts a tumor suppressive effect on precancerous conditions and cancer cells associated with sporadic as well as colitis-associated colorectal cancer. The anti-tumor effect of ferrichrome was mediated by the upregulation of DDIT3, and was superior to that of 5-FU or cisplatin. These results suggest that Lactobacillus brevis-derived ferrichrome may be a candidate anti-tumor drug for the treatment of colorectal neoplasms.
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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。
影响因子：
16.6
作者：
Konishi H;Fujiya M;Tanaka H;Ueno N;Moriichi K;Sasajima J;Ikuta K;Akutsu H;Tanabe H;Kohgo Y
通讯作者：
Kohgo Y
影响因子：
3.5
作者：
Papadakis, ES;Finegan, KG;Tournier, C
通讯作者：
Tournier, C
影响因子：
4.3
作者：
Kim, Jung Han
通讯作者：
Kim, Jung Han
影响因子：
64.5
作者：
Puthalakath, Hamsa;O'Reilly, Lorraine A.;Strasser, Andreas
通讯作者：
Strasser, Andreas
影响因子：
7.1
作者：
Marteau, PR;de Vrese, M;Schrezenmeir, J
通讯作者：
Schrezenmeir, J