Chrysophanol-induced cell death (necrosis) in human lung cancer A549 cells is mediated through increasing reactive oxygen species and decreasing the level of mitochondrial membrane potential.

Abstract

Chrysophanol (1,8-dihydroxy-3-methylanthraquinone) is one of the anthraquinone compounds, and it has been shown to induce cell death in different types of cancer cells. The effects of chrysophanol on human lung cancer cell death have not been well studied. The purpose of this study is to examine chrysophanol-induced cytotoxic effects and also to investigate such influences that involved apoptosis or necrosis in A549 human lung cancer cells in vitro. Our results indicated that chrysophanol decreased the viable A549 cells in a dose- and time-dependent manner. Chrysophanol also promoted the release of reactive oxygen species (ROS) and Ca(2+) and decreased the levels of mitochondria membrane potential (ΔΨm ) and adenosine triphosphate in A549 cells. Furthermore, chrysophanol triggered DNA damage by using Comet assay and DAPI staining. Importantly, chrysophanol only stimulated the cytocheome c release, but it did not activate other apoptosis-associated protein levels including caspase-3, caspase-8, Apaf-1, and AIF. In conclusion, human lung cancer A549 cells treated with chrysophanol exhibited a cellular pattern associated with necrotic cell death and not apoptosis in vitro. © 2012 Wiley Periodicals, Inc. Environ Toxicol 29: 740-749, 2014.

• Authors: Chien-Hang Ni, Chun-Shu Yu, Hsu-Feng Lu, Jai-Sing Yang, Hui-Ying Huang, Po-Yuan Chen, Shin-Hwar Wu, Siu-Wan Ip, Su-Yin Chiang, Jaung-Geng Lin, Jing-Gung Chung
• Journal: Environmental toxicology (Environ Toxicol) Vol. 29 Issue 7 Pg. 740-9 (May 2014) ISSN: 1522-7278 [Electronic] United States
• PMID: 22848001 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2012 Wiley Periodicals, Inc., a Wiley company.

Chemical References

• Anthraquinones
• Antineoplastic Agents
• Reactive Oxygen Species
• Adenosine Triphosphate
• Caspase 3
• Caspase 8
• chrysophanic acid
• Calcium

Topics

• Adenosine Triphosphate (metabolism)
• Anthraquinones (pharmacology)
• Antineoplastic Agents (pharmacology)
• Apoptosis (drug effects)
• Calcium (metabolism)
• Caspase 3 (metabolism)
• Caspase 8 (metabolism)
• Cell Line, Tumor
• Cell Survival (drug effects)
• DNA Damage
• Humans
• Lung Neoplasms (metabolism, pathology)
• Membrane Potential, Mitochondrial (drug effects)
• Necrosis
• Oxidative Stress (drug effects)
• Reactive Oxygen Species (metabolism)
• S Phase Cell Cycle Checkpoints