Andrographolide induces cell cycle arrest at G2/M phase and cell death in HepG2 cells via alteration of reactive oxygen species

Jieliang Li, Hon Yeung Cheung*, Zhiqiang Zhang, Gallant K.L. Chan, David W F FONG

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

114 Citations (Scopus)

Abstract

The cytotoxicity of andrographolide to HepG2 human hepatoma cells was investigated in the present study. Growth of HepG2 cells was affected in the presence of andrographolide with an IC50 of 40.2 μM after 48 h treatment. Flow cytometric analysis and DNA fragmentation assay revealed that andrographolide induced cell cycle arrest at G2/M phase and a late apoptosis of the cells. The occurrence of cell cycle arrest was accompanied by the collapse of mitochondrial membrane potential (MMP) and an intracellular increase of hydrogen peroxide (H2O2) but a decrease of superoxide radicals (O2{radical dot}-) and reduced glutathione. In the treated cells, expression of Bax as well as the transcriptional controller of this pro-apoptotic gene, p53, was upregulated but not other apoptotic proteins such as Bad, Bcl-2 and Bcl-XL. Although the activity of caspase-3, which has direct effect on apoptosis, was also enhanced by the presence of andrographolide, cell death of HepG2 could neither be prevented by a specific inhibitor of capsase-3 nor the pan-caspase inhibitor-zVAD (Val-Ala-Asp), indicating that it was a caspase-independent cell death. Since the overall percentage of apoptotic cells was relatively small throughout the experimental studies, we conclude that the cytotoxic effect of andrographolide on HepG2 cells is primary attributed to the induction of cell cycle arrest via the alteration of cellular redox status.

Original languageEnglish
Pages (from-to)31-44
Number of pages14
JournalEuropean Journal of Pharmacology
Volume568
Issue number1-3
DOIs
Publication statusPublished - 30 Jul 2007

Scopus Subject Areas

  • Pharmacology

User-Defined Keywords

  • Andrographolide
  • Cell cycle arrest
  • Cell death
  • HepG2 cell
  • Mitochondrial membrane potential
  • Reactive oxygen species

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