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

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

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163 Scopus citations

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. Chryso-phanol 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 (ACm) 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.

Original languageEnglish (US)
Pages (from-to)967-976
Number of pages10
JournalMolecular Nutrition and Food Research
Volume54
Issue number7
DOIs
StatePublished - Jul 2010

Keywords

  • Adenosine triphosphate
  • Chrysophanol
  • J5 human liver cancer cells
  • Necrosis
  • Reactive oxygen species

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    Lu, C. C., Yang, J. S., Huang, A. C., Hsia, T. C., Chou, S. T., Kuo, C. L., Lu, H. F., Lee, T. H., Wood, W. G., & Chung, J. G. (2010). Chrysophanol induces necrosis through the production of ROS and alteration of ATP levels in J5 human liver cancer cells. Molecular Nutrition and Food Research, 54(7), 967-976. https://doi.org/10.1002/mnfr.200900265