title: Antibiotic drug levofloxacin inhibits proliferation and induces apoptosis of lung cancer cells through inducing mitochondrial dysfunction and oxidative damage.
abstract: Lung cancer is the leading cause of cancer death worldwide and its clinical management remains challenge. Here, we repurposed antibiotic levofloxacin for lung cancer treatment. We show that levofloxacin is effectively against a panel of lung cancer cell lines via inhibiting proliferation and inducing apoptosis, regardless of cellular origin and genetic pattern, in in vitro cell culture system and in vivo xenograft lung tumor model. Mechanistically, levofloxacin inhibits activities of mitochondrial electron transport chain complex I and III, leading to inhibition of mitochondrial respiration and reduction of ATP production. In addition, levofloxacin significantly increases levels of ROS, mitochondrial superoxide and hydrogen peroxide in vitro and oxidative stress markers (HEL and 4-HNE) in vivo. Antioxidants, such as NAC and vitamin C, prevent the inhibitory effects of levofloxacin, confirming the induction of oxidative damage as the mechanism of its action in lung cancer cells. Our work demonstrates that levofloxacin is a useful addition to the treatment of lung cancer. Our work also suggests that targeting mitochondria may be an alternative therapeutic strategy for lung cancer treatment.
authors: Department of Respiratory Medicine, Ningbo Medical Treatment Center Li Huili Hospital, Ningbo, China.
authors: Meijun
authors: M
authors: Song
authors: Department of Respiratory Medicine, Ningbo Medical Treatment Center Li Huili Hospital, Ningbo, China. Electronic address: smj800722@aliyun.com.
authors: Hongcheng
authors: H
authors: Wu
authors: Department of Respiratory Medicine, Ningbo Medical Treatment Center Li Huili Hospital, Ningbo, China.
authors: Shibo
authors: S
authors: Wu
authors: Department of Respiratory Medicine, Ningbo Medical Treatment Center Li Huili Hospital, Ningbo, China.
authors: Ting
authors: T
authors: Ge
authors: Department of Respiratory Medicine, Ningbo Medical Treatment Center Li Huili Hospital, Ningbo, China.
authors: Guoan
authors: G
authors: Wang
authors: Department of Respiratory Medicine, Ningbo Medical Treatment Center Li Huili Hospital, Ningbo, China.
authors: Yingyan
authors: Y
authors: Zhou
authors: Department of Respiratory Medicine, Ningbo Medical Treatment Center Li Huili Hospital, Ningbo, China.
authors: Shimo
authors: S
authors: Sheng
authors: Department of Respiratory Medicine, Ningbo Medical Treatment Center Li Huili Hospital, Ningbo, China. Electronic address: docjjb201015@126.com.
authors: Jingbo
authors: J
authors: Jiang
mesh_terms: D000447:Aldehydes / Q000378:metabolism; D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D004249:DNA Damage; D004305:Dose-Response Relationship, Drug; D042967:Electron Transport Complex I / Q000378:metabolism; D014450:Electron Transport Complex III / Q000378:metabolism; D006801:Humans; D064704:Levofloxacin / Q000494:pharmacology*; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D016513:Mice, SCID; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D018384:Oxidative Stress / Q000187:drug effects*; D017382:Reactive Oxygen Species / Q000378:metabolism; D047368:Tumor Burden / Q000187:drug effects; D023041:Xenograft Model Antitumor Assays
chemical_list: D000447:Aldehydes; D000903:Antibiotics, Antineoplastic; D017382:Reactive Oxygen Species; D064704:Levofloxacin; D042967:Electron Transport Complex I; D014450:Electron Transport Complex III; C027576:4-hydroxy-2-nonenal
keywords: Drug repurposing; Levofloxacin; Mitochondria; Oxidative damage