title: Tigecycline targets nonsmall cell lung cancer through inhibition of mitochondrial function.
abstract: Nonsmall cell lung cancer (NSCLC) is the most common type of lung cancer with a high mortality rate and still remains therapeutically a challenge. A strategy to target NSCLC is to identify agents that are effective against NSCLC cells while sparing normal cells. We show that tigecycline, an FDA-approved antibiotic drug, preferentially targets NSCLC cells. Tigecycline is effective in inhibiting proliferation and inducing apoptosis of multiple cell lines derived from two common NSCLC subtypes: adenocarcinoma and squamous cell carcinoma. Tigecycline also dose-dependently inhibits colony formation of NSCLC subpopulation of cells with highly proliferative and invasive properties. Compared to NSCLC cells, tigecycline affects proliferation and survival of normal fibroblast cells significantly to a less extent. More importantly, tigecycline significantly inhibits NSCLC tumor growth through decreasing proliferation and increasing apoptosis of tumor cells in vivo. Tigecycline significantly inhibits mitochondrial respiration, mitochondrial membrane potential, and ATP levels and increases reactive oxygen species (ROS), suggesting that tigecycline impairs mitochondrial functions. Our study suggests that tigecycline may be a useful therapeutic agent, and inhibiting mitochondrial functions may represent a new targeted therapy for NSCLC.
authors.affiliation: Department of Oncology, The First People's Hospital of Jining, No.6 Jiankang road, Jining, Shandong Province, China.
authors.forename: Xuefeng
authors.initials: X
authors.lastname: Jia
authors.affiliation: Department of Oncology, Affiliated Hospital of Jining Medical University, No.79 Guhuai road, Jining, Shandong Province, China.
authors.forename: Zhenfang
authors.initials: Z
authors.lastname: Gu
authors.affiliation: Department of Oncology, The First People's Hospital of Jining, No.6 Jiankang road, Jining, Shandong Province, China.
authors.forename: Wenming
authors.initials: W
authors.lastname: Chen
authors.affiliation: Department of Oncology, The First People's Hospital of Jining, No.6 Jiankang road, Jining, Shandong Province, China.
authors.forename: Junbo
authors.initials: J
authors.lastname: Jiao
mesh_terms: D000072283:A549 Cells; D000818:Animals; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000473:pathology; D049109:Cell Proliferation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D016503:Drug Delivery Systems / Q000379:methods*; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000473:pathology; D051379:Mice; D016513:Mice, SCID; D008911:Minocycline / Q000008:administration & dosage / Q000031:analogs & derivatives*; D008928:Mitochondria / Q000187:drug effects* / Q000502:physiology; D000078304:Tigecycline; D047368:Tumor Burden / Q000187:drug effects / Q000502:physiology; D023041:Xenograft Model Antitumor Assays / Q000379:methods
chemical_list: D000078304:Tigecycline; D008911:Minocycline
keywords: NSCLC; Tigecycline; drug repurposing; mitochondrial metabolism