Chrysophanol induces necrosis through the production of ROS and alteration of ATP levels in J5 human liver cancer cells.
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.
Lu
Chi-Cheng
CC
Department of Life Sciences, National Chung Hsing University, Taichung, Taiwan.
Yang
Jai-Sing
JS
Huang
An-Cheng
AC
Hsia
Te-Chun
TC
Chou
Su-Tze
ST
Kuo
Chao-Lin
CL
Lu
Hsu-Feng
HF
Lee
Tsung-Han
TH
Wood
Wellington G
WG
Chung
Jing-Gung
JG
D000255:Adenosine Triphosphate / Q000378:metabolism*; D000880:Anthraquinones / Q000494:pharmacology*; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D061945:Caspase Inhibitors; D020169:Caspases / Q000378:metabolism; D045744:Cell Line, Tumor; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects; D015853:Cysteine Proteinase Inhibitors / Q000494:pharmacology; D045304:Cytochromes c / Q000378:metabolism; D004249:DNA Damage / Q000187:drug effects; D016166:Free Radical Scavengers / Q000494:pharmacology; D006801:Humans; D045022:Lactate Dehydrogenases / Q000378:metabolism; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology*; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D008930:Mitochondria, Liver / Q000187:drug effects / Q000201:enzymology; D009336:Necrosis / Q000139:chemically induced; D009994:Osmolar Concentration; D010718:Phosphatidylserines / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism*; D013997:Time Factors
D000880:Anthraquinones; D000972:Antineoplastic Agents, Phytogenic; D061945:Caspase Inhibitors; D015853:Cysteine Proteinase Inhibitors; D016166:Free Radical Scavengers; D010718:Phosphatidylserines; D017382:Reactive Oxygen Species; D000255:Adenosine Triphosphate; D045304:Cytochromes c; D045022:Lactate Dehydrogenases; D020169:Caspases; C027113:chrysophanic acid