Chrysophanol-induced necrotic-like cell death through an impaired mitochondrial ATP synthesis in Hep3B human liver cancer cells

Chien Hang Ni, Po Yuan Chen, Hsu Feng Lu, Jai Sing Yang, Hui Ying Huang, Shin Hwar Wu, Siu Wan Ip, Chin Tung Wu, Su Yin Chiang, Jaung Geng Lin, W. Gibson Wood, Jing Gung Chung

Research output: Contribution to journalArticlepeer-review

23 Scopus citations

Abstract

Liver cancer is the most common form of cancer in Taiwan and it usually responds to chemotherapy. However, patients often have side effects to the chemotherapeutic drugs. Thus new agents are urgently required to treat liver cancer. Chrysophanol, one of the anthraquinone derivatives, was reported to inhibit some human cancer cell growth which may be due to the induction of apoptosis similar to other anthraquinone derivatives though such actions have not been reported. In the present study, we reported that chrysophanol inhibits cell growth in Hep3B liver cancer cells based on the following observations: 1) induc cell morphological changes; 2) decreased percentage of viable cells; 3) induced S phase arrest of cell cycle progression; 4) induced DNA damage as measured by comet assay and DAPI staining. Chrysophanolinduced cell death however, seems to be related to necrotic processes rather than typical apoptosis. Chrysophanol induced reactive oxygen species and Ca2+ production and decreased mitochondrial membrane potential (ΔΨm) and ATP levels in Hep3B cells. No effects were observed on known protein regulators of apoptosis such as Bax and Bcl-2. Chrysophanolinduced cell death took place independently of caspase-8 and -9. Based on our findings, we propose that chrysophanol reduces cellular ATP levels causing a drop in energy resulting in necrotic-like cell death.

Original languageEnglish (US)
Pages (from-to)887-895
Number of pages9
JournalArchives of Pharmacal Research
Volume35
Issue number5
DOIs
StatePublished - May 2012

Bibliographical note

Funding Information:
This work was supported by a research grant CMU100-NSC-01 from China Medical University, Taichung, Taiwan.

Copyright:
Copyright 2013 Elsevier B.V., All rights reserved.

Keywords

  • Chrysophanol
  • Human liver cancer cells (Hep3B)
  • Mitochondrial membrane potential
  • Necrosis
  • Reactive oxygen species

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