Bufalin induces apoptosis in vitro and has Antitumor activity against human lung cancer xenografts in vivo

  • Environ Toxicol. 2017 Apr;32(4):1305-1317. doi: 10.1002/tox.22325.
Shin-Hwar Wu  1  2 ,  Da-Tian Bau  3 ,  Yung-Ting Hsiao  4 ,  Kung-Wen Lu  5 ,  Te-Chun Hsia  6 ,  Jin-Cherng Lien  7 ,  Yang-Ching Ko  1 ,  Wu-Huei Hsu  8  6 ,  Su-Tso Yang  9  10 ,  Yi-Ping Huang  11 ,  Jing-Gung Chung  4  12
Affiliations
  • 1. Institute of Clinical Medical Science, China Medical University, Taichung, 404, Taiwan.
  • 2. Division of Critical Care Medicine, Department of Medicine, Changhua Christian Hospital, Changhua, 500, Taiwan.
  • 3. Terry Fox Cancer Research Laboratory, Department of Medical Research, China Medical University Hospital, Taichung, 404, Taiwan.
  • 4. Department of Biological Science and Technology, China Medical University, Taichung, 404, Taiwan.
  • 5. College of Chinese Medicine, School of Post-Baccalaureate Chinese Medicine, China Medical University, Taichung, 404, Taiwan.
  • 6. Department of Internal Medicine, China Medical University Hospital, Taichung, 404, Taiwan.
  • 7. School of Pharmacy, China Medical University, Taichung, 40402, Taiwan.
  • 8. Department of Internal Medicine, China Medical University, Taichung, 404, Taiwan.
  • 9. Department of Radiology, China Medical University Hospital, Taichung, 404, Taiwan.
  • 10. School of Chinese Medicine, China Medical University, Taichung, 404, Taiwan.
  • 11. Department of Physiology, China Medical University, Taichun, 404, Taiwan.
  • 12. Department of Biotechnology, Asia University, Taichung, 404, Taiwan.
PMID: 27444971 DOI: 10.1002/tox.22325
Abstract

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.

Keywords
animal models; apoptosis; bufalin; lung neoplasm.
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