Bufalin induces apoptosisin vitroand has Antitumor activity against human lung cancer xenograftsin vivo
Autor: | Jing Gung Chung, Yang Ching Ko, Su Tso Yang, Te Chun Hsia, Yung Ting Hsiao, Shin Hwar Wu, Kung Wen Lu, Jin-Cherng Lien, Da Tian Bau, Yi Ping Huang, Wu-Huei Hsu |
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Rok vydání: | 2016 |
Předmět: |
0301 basic medicine
Health Toxicology and Mutagenesis Bufalin Caspase 3 General Medicine Management Monitoring Policy and Law Pharmacology Biology Toxicology Caspase 8 respiratory tract diseases 03 medical and health sciences 030104 developmental biology 0302 clinical medicine Apoptosis Cell culture In vivo 030220 oncology & carcinogenesis Cancer cell Cytotoxicity |
Zdroj: | Environmental Toxicology. 32:1305-1317 |
ISSN: | 1520-4081 |
Popis: | Bufalin has been shown to be effective against a variety of cancer cells, but its role in lung cancer has never been studied in an animal model. In this study, we evaluated bufalin effects in a human lung cancer cell line NCI-H460 both in vitro and in vivo. Bufalin caused significant cytotoxicity in NCI-H460 cells at a concentration as low as 1 μM. DNA condensation was observed in bufalin-treated cells in a dose-dependent manner. Mitochondrial membrane potential (ΔΨm ) was reduced and reactive oxygen species (ROS) were increased in bufalin-treated NCI-H460 cells. Levels of several proapoptotic proteins such as Fas, Fas-ligand, cytochrome c, apoptosis protease activating factor-1, endonuclease G, caspase-3 and caspase-9 were increased after bufalin treatment. At the same time, anti-apoptotic B-cell lymphoma 2 protein levels were reduced. Bufalin decreased glucose regulated protein-78 gene expression but increased growth arrest- and DNA damage-inducible 153 gene expression. Bufalin injected intraperitoneally in a dose-dependent manner reduced tumor size in BALB/C nu/nu mice implanted with NCI-H460 cells. Bufalin injection did not produce significant drug-related toxicity in experimental animals except at a high dose (0.4 mg kg-1 ). In conclusion, low concentrations of bufalin can induce apoptosis in the human lung cancer cell line NCI-H460 in vitro. Bufalin also reduced tumor size in mice injected with NCI-H460 cells without significant drug-related toxicity. These results indicate that bufalin may have potential to be developed as an agent for treating human non-small cell lung cancer. © 2016 Wiley Periodicals, Inc. Environ Toxicol 32: 1305-1317, 2017. |
Databáze: | OpenAIRE |
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