Ceftriaxone, an FDA-approved cephalosporin antibiotic, suppresses lung cancer growth by targeting Aurora B

被引:32
作者
Li, Xiang [2 ]
Li, Haitao
Li, Shengqing
Zhu, Feng
Kim, Dong Joon
Xie, Hua
Li, Yan
Nadas, Janos
Oi, Naomi
Zykova, Tatyana A.
Yu, Dong Hoon
Lee, Mee-Hyun
Kim, Myoung Ok
Wang, Lei
Ma, Weiya
Lubet, Ronald A. [3 ]
Bode, Ann M.
Dong, Ziming [2 ]
Dong, Zigang [1 ]
机构
[1] Univ Minnesota, Hormel Inst, Mayo Clin, Austin, MN 55912 USA
[2] Zhengzhou Univ, Basic Med Coll, Zhengzhou 450001, Henan, Peoples R China
[3] NCI, Bethesda, MD 20892 USA
基金
美国国家卫生研究院;
关键词
FATTY-ACID SYNTHASE; CELL-GROWTH; HISTONE H3; KINASE INHIBITOR; EXPRESSION; PHOSPHORYLATION; OVEREXPRESSION; PHARMACOLOGY; ACTIVATION; CARCINOMA;
D O I
10.1093/carcin/bgs283
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Ceftriaxone, an FDA-approved third-generation cephalosporin antibiotic, has antimicrobial activity against both gram-positive and gram-negative organisms. Generally, ceftriaxone is used for a variety of infections such as community-acquired pneumonia, meningitis and gonorrhea. Its primary molecular targets are the penicillin-binding proteins. However, other activities of ceftriaxone remain unknown. Herein, we report for the first time that ceftriaxone has antitumor activity in vitro and in vivo. Kinase profiling results predicted that Aurora B might be a potential ooff' target of ceftriaxone. Pull-down assay data confirmed that ceftriaxone could bind with Aurora B in vitro and in A549 cells. Furthermore, ceftriaxone (500 M) suppressed anchorage-independent cell growth by targeting Aurora B in A549, H520 and H1650 lung cancer cells. Importantly, in vivo xenograft animal model results showed that ceftriaxone effectively suppressed A549 and H520 lung tumor growth by inhibiting Aurora B. These data suggest the anticancer efficacy of ceftriaxone for the treatment of lung cancers through its inhibition of Aurora B.
引用
收藏
页码:2548 / 2557
页数:10
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