title: Activation of multiple apoptotic pathways in human nasopharyngeal carcinoma cells by the prenylated isoflavone, osajin.
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.
authors.affiliation: Department of Life Sciences, National Central University, Taoyuan, Taiwan, Republic of China.
authors.forename: Tsung-Teng
authors.initials: TT
authors.lastname: Huang
authors.forename: Fu-Guo
authors.initials: FG
authors.lastname: Liu
authors.forename: Chia-Fong
authors.initials: CF
authors.lastname: Wei
authors.forename: Chia-Chen
authors.initials: CC
authors.lastname: Lu
authors.forename: Chang-Chieh
authors.initials: CC
authors.lastname: Chen
authors.forename: Hung-Chi
authors.initials: HC
authors.lastname: Lin
authors.forename: David M
authors.initials: DM
authors.lastname: Ojcius
authors.forename: Hsin-Chih
authors.initials: HC
authors.lastname: Lai
mesh_terms: D017209:Apoptosis; D045744:Cell Line, Tumor; D000091342:Endoplasmic Reticulum Chaperone BiP; D006801:Humans; D007529:Isoflavones / Q000494:pharmacology*; D008564:Membrane Potentials / Q000187:drug effects; D008928:Mitochondria / Q000187:drug effects; D009303:Nasopharyngeal Neoplasms / Q000378:metabolism / Q000473:pathology*; D010936:Plant Extracts / Q000494:pharmacology*
chemical_list: D000091342:Endoplasmic Reticulum Chaperone BiP; C000717247:HSPA5 protein, human; D007529:Isoflavones; D010936:Plant Extracts; C485800:osajin