Cardamonin Induces Cell Cycle Arrest, Apoptosis and Alters Apoptosis Associated Gene Expression in WEHI-3 Mouse Leukemia Cells

Nien-Chieh Liao, Yung-Luen Shih, Jiann-Shang Chou, Kuo-Wei Chen, Yung-Liang Chen, Mei-Hui Lee, Shu-Fen Peng, Sy-Jye Leu, Jing-Gung Chung

Research output: Contribution to journalArticlepeer-review

13 Citations (Scopus)

Abstract

Cardamonin, the chalcone class, is one of the natural components from the spicy herbaceous plant (Alpinia conchigera Griff) and has anticancer activities in many human cancer cell lines. There is, however, no information to show that cardamonin induces cell apoptosis and alters apoptosis associated gene expressions in mouse leukemia cells. Thus, we investigated the effects of cardamonin on the apoptotic cell death and associated gene expression in mouse leukemia WEHI-3 cells in vitro. Results indicated that cardamonin decreased total viable cell number via induced cell morphological changes and apoptotic cell death in WEHI-3 cells that were assay by contrast-phase microscopy and flow cytometry examinations, respectively. The flow cytometry assay indicated that cardamonin increased reactive oxygen species (ROS) and Ca production, decreased the levels of mitochondrial membrane potential ( mÞ and increased caspase-3, -8 and -9 activities in WEHI-3 cells. Western blotting was performed to analyze expression of relevant pro- and anti-apoptotic proteins and results showed that cardamonin decreased anti-apoptotic protein of Bcl-2 but increased pro-apoptotic protein of Bax in WEHI-3 cells. Furthermore, cardamonin increased cytochrome c, AIF and Endo G release, increased GRP78, caspase-12 that were associated with ER stress and increased Fas, Fas-Ligand and FADD expression. Furthermore, cardamonin increased the gene expressions of DAP (death-associated protein), TMBIM4 transmembrane (BAX inhibitor motif containing 4), ATG5 (autophagy related 5) but decreased the gene expression of DDIT3 (DNA-damage inducible transcript 3), DDIT4 (DNA-damage-inducible transcript 4), BAG6 (BCL2-asso-ciated athanogene 6), BCL2L13 [BCL2-like 13 (apoptosis facilitator)] and BRAT1 (BRCA1-associated ATM activator 1) that are associated with apoptosis pathways. Based on those findings, we may suggest cardamonin induced apoptotic cell death through Fas and Fas-Ligand-, caspase- and mitochondria-dependently pathways and also affects the apoptotic gene expression in WEHI-3 cells in vitro.

Original languageEnglish
Pages (from-to)635-656
Number of pages22
JournalThe American journal of Chinese medicine
Volume47
Issue number3
Early online dateApr 25 2019
DOIs
Publication statusPublished - 2019

Keywords

  • Apoptosis
  • CDNA
  • Cardamonin
  • Gene Expression
  • Mouse Leukemia WEHI-3 Cells
  • Apoptosis/drug effects
  • Gene Expression Regulation, Developmental/drug effects
  • Chalcones/pharmacology
  • Animals
  • Cell Line, Tumor
  • Cell Cycle Checkpoints/drug effects
  • Mice
  • Leukemia/genetics

ASJC Scopus subject areas

  • Complementary and alternative medicine

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