In:
International Journal of Molecular Sciences, MDPI AG, Vol. 24, No. 2 ( 2023-01-11), p. 1469-
Abstract:
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.
Type of Medium:
Online Resource
ISSN:
1422-0067
DOI:
10.3390/ijms24021469
Language:
English
Publisher:
MDPI AG
Publication Date:
2023
detail.hit.zdb_id:
2019364-6
SSG:
12
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