Optimized Antimicrobial Peptide Jelleine-I Derivative Br-J-I Inhibits Fusobacterium Nucleatum to Suppress Colorectal Cancer Progression.
Optimized Antimicrobial Peptide Jelleine-I Derivative Br-J-I Inhibits Fusobacterium Nucleatum to Suppress Colorectal Cancer Progression.
复制标题
优化的抗菌肽 Jelleine-I 衍生物 Br-J-I 可抑制核酸镰刀菌，从而抑制结直肠癌的发展。
DOI：
10.3390/ijms24021469
复制
发表时间：
2023-01-11
影响因子：
5.6
通讯作者：
He, Feng
中科院分区：
文献类型：
--
作者：
Jia, Fengjing;Yu, Qun;Wang, Ruolei;Zhao, Ling;Yuan, Fuwen;Guo, Haidong;Shen, Yunhui;He, Feng
关键词：
结直肠癌(CRC)发病率高、病死率高、病因复杂，是世界范围内的主要健康负担。核梭杆菌(FN)是一种革兰氏阴性厌氧菌，在30%的结直肠癌患者中发现，它促进结直肠癌的发生、转移和化疗耐药。对于不断增加的儿童权利公约负担，有效的抗菌治疗是一个尚未得到满足的需求。抗菌肽代表了一类新的抗菌药物。在我们以前的研究中，我们对Jelleine-I(J-I)进行了构效研究，并鉴定了几个卤代J-I衍生物Cl-J-I，BrJ-I和I-J-I。为了确定这些J-I衍生物是否可以作为治疗细菌相关性结直肠癌的新方法，我们在这里测试了这些AMP对FN的抗菌活性以及它们对结直肠癌发生的影响。我们发现BR-J-I具有最高的抗FN活性，并且BR-J-I可能针对膜相关FADA来破坏FN膜。更重要的是，FN促进了CRC细胞来源的异种移植瘤的生长。BR-J-I抑制FN负荷、结肠炎和FN诱导的CRC生长。值得注意的是，BR-J-I比普通抗生素甲硝唑具有更好的抗结直肠癌作用，并且BR-J-I增敏化疗药物5-氟尿嘧啶的杀伤作用。提示BR-J-I可作为结直肠癌治疗的辅助药物，以AMPS为基础的联合治疗是未来结直肠癌治疗的新策略。
Colorectal cancer (CRC) is a major health burden worldwide due to its high morbidity, mortality, and complex etiology. Fusobacterium nucleatum (Fn), a Gram-negative anaerobe found in 30% of CRC patients, promotes CRC carcinogenesis, metastasis, and chemoresistance. Effective antimicrobial treatment is an unmet need for the rising CRC burden. Antimicrobial peptides (AMPs) represent a new class of antimicrobial drugs. In our previous study, we did the structure-activity study of Jelleine-I (J-I) and identified several halogenated J-I derivatives Cl-J-I, Br-J-I, and I-J-I. To determine whether those J-I derivatives can be a new therapy for bacterial-associated CRC, here we tested the antibacterial activities of these AMPs against Fn and their effects on CRC development. We found that Br-J-I showed the highest anti-Fn activity and Br-J-I may target membrane-associated FadA for Fn membrane disruption. More importantly, Fn promoted the growth of CRC cells-derived xenograft tumors. Br-J-I suppressed Fn load, colon inflammation, and Fn-induced CRC growth. Of note, Br-J-I induced better anti-CRC effects than common antibiotic metronidazole and Br-J-I sensitized the cancer-killing effect of chemotherapy drug 5-fluorouracil. These results suggest that Br-J-I could be considered as an adjunctive agent for CRC treatment and AMPs-based combination treatment is a new strategy for CRC in the future.
登录
查看更多内容
影响因子：
16.6
作者：
Arthur, Janelle C.;Gharaibeh, Raad Z.;Muehlbauer, Marcus;Perez-Chanona, Ernesto;Uronis, Joshua M.;McCafferty, Jonathan;Fodor, Anthony A.;Jobin, Christian
通讯作者：
Jobin, Christian
影响因子：
1.7
作者：
Chacko, Shinu;Samanta, Subir
通讯作者：
Samanta, Subir
影响因子：
64.8
作者：
Jumper J;Evans R;Pritzel A;Green T;Figurnov M;Ronneberger O;Tunyasuvunakool K;Bates R;Žídek A;Potapenko A;Bridgland A;Meyer C;Kohl SAA;Ballard AJ;Cowie A;Romera-Paredes B;Nikolov S;Jain R;Adler J;Back T;Petersen S;Reiman D;Clancy E;Zielinski M;Steinegger M;Pacholska M;Berghammer T;Bodenstein S;Silver D;Vinyals O;Senior AW;Kavukcuoglu K;Kohli P;Hassabis D
通讯作者：
Hassabis D
DOI：
10.1186/s13046-020-01677-w
发表时间：
2020-09-29
期刊：
Journal of experimental & clinical cancer research : CR
影响因子：
--
作者：
Guo P;Tian Z;Kong X;Yang L;Shan X;Dong B;Ding X;Jing X;Jiang C;Jiang N;Yu Y
通讯作者：
Yu Y
影响因子：
3
作者：
Jia, Fengjing;Zhang, Yi;Wang, Kairong
通讯作者：
Wang, Kairong