Chrysophanol induces necrosis through the production of ROS and alteration of ATP levels in J5 human liver cancer cells.

Abstract

Anthraquinone compounds have been shown to induce apoptosis in different cancer cell types. Effects of chrysophanol, an anthraquinone compound, on cancer cell death have not been well studied. The goal of this study was to examine if chrysophanol had cytotoxic effects and if such effects involved apoptosis or necrosis in J5 human liver cancer cells. Chrysophanol induced necrosis in J5 cells in a dose- and time-dependent manner. Non-apoptotic cell death was induced by chrysophanol in J5 cells and was characterized by caspase independence, delayed externalization of phosphatidylserine and plasma membrane disruption. Blockage of apoptotic induction by a general caspase inhibitor (z-VAD-fmk) failed to protect cells against chrysophanol-induced cell death. The levels of reactive oxygen species production and loss of mitochondrial membrane potential (DeltaPsi(m)) were also determined to assess the effects of chrysophanol. However, reductions in adenosine triphosphate levels and increases in lactate dehydrogenase activity indicated that chrysophanol stimulated necrotic cell death. In summary, human liver cancer cells treated with chrysophanol exhibited a cellular pattern associated with necrosis and not apoptosis.

• Authors: Chi-Cheng Lu, Jai-Sing Yang, An-Cheng Huang, Te-Chun Hsia, Su-Tze Chou, Chao-Lin Kuo, Hsu-Feng Lu, Tsung-Han Lee, Wellington G Wood, Jing-Gung Chung
• Journal: Molecular nutrition & food research (Mol Nutr Food Res) Vol. 54 Issue 7 Pg. 967-76 (Jul 2010) ISSN: 1613-4133 [Electronic] Germany
• PMID: 20169580 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Anthraquinones
• Antineoplastic Agents, Phytogenic
• Caspase Inhibitors
• Cysteine Proteinase Inhibitors
• Free Radical Scavengers
• Phosphatidylserines
• Reactive Oxygen Species
• Adenosine Triphosphate
• Cytochromes c
• Lactate Dehydrogenases
• Caspases
• chrysophanic acid

Topics

• Adenosine Triphosphate (metabolism)
• Anthraquinones (pharmacology)
• Antineoplastic Agents, Phytogenic (pharmacology)
• Caspase Inhibitors
• Caspases (metabolism)
• Cell Line, Tumor
• Cell Membrane (drug effects, metabolism)
• Cell Survival (drug effects)
• Cysteine Proteinase Inhibitors (pharmacology)
• Cytochromes c (metabolism)
• DNA Damage (drug effects)
• Free Radical Scavengers (pharmacology)
• Humans
• Lactate Dehydrogenases (metabolism)
• Liver Neoplasms (drug therapy, metabolism, pathology)
• Membrane Potential, Mitochondrial (drug effects)
• Mitochondria, Liver (drug effects, enzymology)
• Necrosis (chemically induced)
• Osmolar Concentration
• Phosphatidylserines (metabolism)
• Reactive Oxygen Species (metabolism)
• Time Factors