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

• Published in: Carcinogenesis (New York) Vol. 33; no. 12; pp. 2548 - 2557
• Main Authors: XIANG LI, HAITAO LI, DONG HOON YU, LEE, Mee-Hyun, MYOUNG OK KIM, LEI WANG, WEIYA MA, LUBET, Ronald A, BODE, Ann M, ZIMING DONG, ZIGANG DONG, SHENGQING LI, FENG ZHU, DONG JOON KIM, HUA XIE, YAN LI, NADAS, Janos, OI, Naomi, ZYKOVA, Tatyana A
• Format: Journal Article
• Language: English
• Published: Oxford Oxford University Press 01.12.2012
• Subjects: Animal models; Animals; Anti-Bacterial Agents - pharmacology; Antibacterial agents; Antibiotics. Antiinfectious agents. Antiparasitic agents; Aurora Kinase B; Aurora Kinases; Biological and medical sciences; Carcinogenesis, carcinogens and anticarcinogens; Ceftriaxone - pharmacology; Cell Line, Tumor; Epidermal Growth Factor - pharmacology; Humans; Lung Neoplasms - drug therapy; Lung Neoplasms - enzymology; Lung Neoplasms - pathology; Medical sciences; Mice; Original Manuscript; Pharmacology. Drug treatments; Pneumology; Protein-Serine-Threonine Kinases - antagonists & inhibitors; Tumors; Tumors of the respiratory system and mediastinum; Lung disease; Targeting; Respiratory disease; Growth; β-Lactams; Lung cancer; Malignant tumor; Ceftriaxone; Bronchopulmonary; Serine/threonine-protein kinase 12; Antibiotic; Target; Cephalosporin derivatives; Bronchus disease; Antibacterial agent; Cancer
• ISSN: 0143-3334; 1460-2180
• DOI: 10.1093/carcin/bgs283

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.