Activation of multiple apoptotic pathways in human nasopharyngeal carcinoma cells by the prenylated isoflavone, osajin

Tsung Teng Huang, Fu Guo Liu, Chia Fong Wei, Chia Chen Lu, Chang Chieh Chen, Hung Chi Lin, David M. Ojcius, Hsin Chih Lai

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25 Scopus citations

Abstract

Osajin is a prenylated isoflavone showing antitumor activity in different tumor cell lines. The underlying mechanism of osajin-induced cancer cell death is not clearly understood. In the present study, the mechanisms of osajin-induced cell death of human nasopharyngeal carcinoma (NPC) cells were explored. Osajin was found to significantly induce apoptosis of NPC cells in a dose- and time-dependent manner. Multiple molecular effects were observed during osajin treatment including a significant loss of mitochondrial transmembrane potential, release of cytochrome c into the cytosol, enhanced expression of Fas ligand (FasL), suppression of glucose-regulated protein 78 kDa (GRP78), and activation of caspases-9, -8, -4 and -3. In addition, up-regulation of proapoptotic Bax protein and down-regulation of antiapoptotic Bcl-2 protein were also observed. Taken together, osajin induces apoptosis in human NPC cells through multiple apoptotic pathways, including the extrinsic death receptor pathway, and intrinsic pathways relying on mitochondria and endoplasmic reticulum stress. Thus, osajin could be developed as a new effective and chemopreventive compound for human NPC.

Original languageEnglish
Article numbere18308
JournalPLoS ONE
Volume6
Issue number4
DOIs
StatePublished - 2011

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