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

Xiang Li, Haitao Li, Shengqing Li, Feng Zhu, Dong Joon Kim, Hua Xie, Yan Li, Janos Nadas, Naomi Oi, Tatyana A. Zykova, Dong Hoon Yu, Mee Hyun Lee, Myoung Ok Kim, Lei Wang, Weiya Ma, Ronald A. Lubet, Ann M. Bode, Ziming Dong, Zigang Dong

Research output: Contribution to journalArticlepeer-review

19 Scopus citations

Abstract

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 'off' target of ceftriaxone. Pull-down assay data confirmed that ceftriaxone could bind with Aurora B in vitro and in A549 cells. Furthermore, ceftriaxone (500 μM) 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.

Original languageEnglish (US)
Article numberbgs283
Pages (from-to)2548-2557
Number of pages10
JournalCarcinogenesis
Volume33
Issue number12
DOIs
StatePublished - Dec 2012

Bibliographical note

Funding Information:
The Hormel Foundation and National Institutes of Health (R37 CA081064, CA120388, ES016548, CA0227501); National Cancer Institute Contract No. HHSN-261200533001C-NO1-CN-53301.

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