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.