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

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.

• Authors: Shin-Hwar Wu, Da-Tian Bau, Yung-Ting Hsiao, Kung-Wen Lu, Te-Chun Hsia, Jin-Cherng Lien, Yang-Ching Ko, Wu-Huei Hsu, Su-Tso Yang, Yi-Ping Huang, Jing-Gung Chung
• Journal: Environmental toxicology (Environ Toxicol) Vol. 32 Issue 4 Pg. 1305-1317 (Apr 2017) ISSN: 1522-7278 [Electronic] United States
• PMID: 27444971 (Publication Type: Journal Article)
• Copyright: © 2016 Wiley Periodicals, Inc.

Chemical References

• Antineoplastic Agents
• Apoptosis Regulatory Proteins
• Bufanolides
• Chromatin
• Endoplasmic Reticulum Chaperone BiP
• FASLG protein, human
• Fas Ligand Protein
• Heat-Shock Proteins
• Reactive Oxygen Species
• Caspase 3
• Caspase 8
• Caspase 9
• bufalin

Topics

• Animals
• Antineoplastic Agents (therapeutic use, toxicity)
• Apoptosis (drug effects)
• Apoptosis Regulatory Proteins (metabolism)
• Bufanolides (therapeutic use, toxicity)
• Carcinoma, Non-Small-Cell Lung (drug therapy, metabolism, pathology)
• Caspase 3 (metabolism)
• Caspase 8 (metabolism)
• Caspase 9 (metabolism)
• Cell Line, Tumor
• Chromatin (drug effects, metabolism)
• DNA Damage (drug effects)
• Disease Models, Animal
• Endoplasmic Reticulum Chaperone BiP
• Fas Ligand Protein (metabolism)
• Heat-Shock Proteins (genetics, metabolism)
• Humans
• Lung Neoplasms (drug therapy, metabolism, pathology)
• Membrane Potential, Mitochondrial (drug effects)
• Mice
• Mice, Inbred BALB C
• Mice, Nude
• Reactive Oxygen Species (metabolism)
• Transplantation, Heterologous