Apoptotic cell death by the novel natural compound, cinobufotalin

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

研究成果: Article査読

27 被引用数 (Scopus)

抄録

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.

本文言語English
ページ(範囲)154-160
ページ数7
ジャーナルChemico-Biological Interactions
199
3
DOI
出版ステータスPublished - 2012 9月 30

ASJC Scopus subject areas

  • 毒物学

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