Apoptotic cell death by the novel natural compound, cinobufotalin

Heba Emam, Qing Li Zhao, Yukihiro Furusawa, Alaa Refaat, Kanwal Ahmed, Makoto Kadowaki, Takashi Kondo

Research output: Contribution to journalArticle

23 Citations (Scopus)

Abstract

Cinobufotalin (CB), one of the bufadienolides prepared from toad venom, was investigated for its cytotoxicity, and the underneath mechanism involved. We primarily utilized DNA fragmentation assay and microscopic observation to assess the effect of various doses of CB in human lymphoma U937 cells. Following that, we investigated other parameters involved in cell death mechanism such as reactive oxygen species (ROS), mitochondrial membrane potential (MMP), and apoptotic proteins activation. HeLa cells were concomitantly used to generalize the data observed. Our results show that CB caused significant DNA fragmentation, decrease of MMP, and an increase in the intracellular Ca 2+ ion and ROS production. In addition, CB induced upregulation of Fas protein, proteolytic activation of cytochrome c, caspase-2, -3, -8 and -9 together with the activation of Bid and Bax. Our findings were further validated using either Fas/FasL antagonist or pan-caspase inhibitor to significantly inhibit CB-induced DNA fragmentation. In our study, we suggest that CB induces caspase dependent cell death in U937 cells, and that Fas plays a role in CB-induced apoptosis. Altogether, our data provides novel insights of the mechanism of action of CB and its potential as a future chemotherapeutic agent.

Original languageEnglish
Pages (from-to)154-160
Number of pages7
JournalChemico-Biological Interactions
Volume199
Issue number3
DOIs
Publication statusPublished - 2012 Sep 30

Keywords

  • Apoptosis
  • Ca
  • Cinobufotalin
  • Fas
  • Mitochondria
  • Phosphatidylserine

ASJC Scopus subject areas

  • Toxicology

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    Emam, H., Zhao, Q. L., Furusawa, Y., Refaat, A., Ahmed, K., Kadowaki, M., & Kondo, T. (2012). Apoptotic cell death by the novel natural compound, cinobufotalin. Chemico-Biological Interactions, 199(3), 154-160. https://doi.org/10.1016/j.cbi.2012.07.005