title: Ceftriaxone, an FDA-approved cephalosporin antibiotic, suppresses lung cancer growth by targeting Aurora B.
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.
authors.affiliation: The Hormel Institute, University of Minnesota,  Austin, Minnesota, USA.
authors.forename: Xiang
authors.initials: X
authors.lastname: Li
authors.forename: Haitao
authors.initials: H
authors.lastname: Li
authors.forename: Shengqing
authors.initials: S
authors.lastname: Li
authors.forename: Feng
authors.initials: F
authors.lastname: Zhu
authors.forename: Dong Joon
authors.initials: DJ
authors.lastname: Kim
authors.forename: Hua
authors.initials: H
authors.lastname: Xie
authors.forename: Yan
authors.initials: Y
authors.lastname: Li
authors.forename: Janos
authors.initials: J
authors.lastname: Nadas
authors.forename: Naomi
authors.initials: N
authors.lastname: Oi
authors.forename: Tatyana A
authors.initials: TA
authors.lastname: Zykova
authors.forename: Dong Hoon
authors.initials: DH
authors.lastname: Yu
authors.forename: Mee-Hyun
authors.initials: MH
authors.lastname: Lee
authors.forename: Myoung Ok
authors.initials: MO
authors.lastname: Kim
authors.forename: Lei
authors.initials: L
authors.lastname: Wang
authors.forename: Weiya
authors.initials: W
authors.lastname: Ma
authors.forename: Ronald A
authors.initials: RA
authors.lastname: Lubet
authors.forename: Ann M
authors.initials: AM
authors.lastname: Bode
authors.forename: Ziming
authors.initials: Z
authors.lastname: Dong
authors.forename: Zigang
authors.initials: Z
authors.lastname: Dong
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D064107:Aurora Kinase B; D064127:Aurora Kinases; D002443:Ceftriaxone / Q000494:pharmacology*; D045744:Cell Line, Tumor; D004815:Epidermal Growth Factor / Q000494:pharmacology; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology; D051379:Mice; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors*
chemical_list: D000900:Anti-Bacterial Agents; D004815:Epidermal Growth Factor; D002443:Ceftriaxone; C576921:AURKB protein, human; C576924:Aurkb protein, mouse; D064107:Aurora Kinase B; D064127:Aurora Kinases; D017346:Protein Serine-Threonine Kinases