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

• Published in: Molecular nutrition & food research Vol. 54; no. 7; pp. 967 - 976
• Main Authors: Lu, Chi-Cheng, Yang, Jai-Sing, Huang, An-Cheng, Hsia, Te-Chun, Chou, Su-Tze, Kuo, Chao-Lin, Lu, Hsu-Feng, Lee, Tsung-Han, Wood, Wellington G, Chung, Jing-Gung
• Format: Journal Article
• Language: English
• Published: Weinheim Wiley-VCH Verlag 01.07.2010; WILEY-VCH Verlag; WILEY‐VCH Verlag; Wiley
• Subjects: Adenosine triphosphate; Adenosine Triphosphate - metabolism; Anthraquinones; Anthraquinones - pharmacology; Antineoplastic Agents, Phytogenic; Antineoplastic Agents, Phytogenic - pharmacology; apoptosis; Biological and medical sciences; Caspase Inhibitors; Caspases; Caspases - metabolism; Cell Line, Tumor; Cell Membrane; Cell Membrane - drug effects; Cell Membrane - metabolism; Cell Survival; Cell Survival - drug effects; chemically induced; Chrysophanol; Cysteine Proteinase Inhibitors; Cysteine Proteinase Inhibitors - pharmacology; Cytochromes c; Cytochromes c - metabolism; cytotoxicity; DNA Damage; DNA Damage - drug effects; drug effects; drug therapy; enzymology; Food industries; Free Radical Scavengers; Free Radical Scavengers - pharmacology; Fundamental and applied biological sciences. Psychology; hepatocytes; Humans; J5 human liver cancer cells; lactate dehydrogenase; Lactate Dehydrogenases; Lactate Dehydrogenases - metabolism; Liver Neoplasms; Liver Neoplasms - drug therapy; Liver Neoplasms - metabolism; Liver Neoplasms - pathology; membrane potential; Membrane Potential, Mitochondrial; Membrane Potential, Mitochondrial - drug effects; metabolism; Mitochondria, Liver; Mitochondria, Liver - drug effects; Mitochondria, Liver - enzymology; Necrosis; Necrosis - chemically induced; Osmolar Concentration; pathology; pharmacology; Phosphatidylserines; Phosphatidylserines - metabolism; plasma membrane; Reactive oxygen species; Reactive Oxygen Species - metabolism; Time Factors; Human; Oxygen; Reactive oxygen species; Liver; Alteration; Triphosphates; Malignant tumor; Necrosis; J5 human liver cancer cells; Production; ATP; Species; Adenosine triphosphate; Chrysophanol; Cancer
• ISSN: 1613-4125; 1613-4133; 1613-4133
• DOI: 10.1002/mnfr.200900265

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 (ΔΨm) 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.