activation of multiple apoptotic pathways in human nasopharyngeal carcinoma cells by the prenylated isoflavone, osajin激活多种凋亡通路在人类鼻咽癌细胞prenylated异黄酮,osajin.pdfVIP

Activation of Multiple Apoptotic Pathways in Human Nasopharyngeal Carcinoma Cells by the Prenylated Isoflavone, Osajin 1 1 2 3 2 2 Tsung-Teng Huang , Fu-Guo Liu *, Chia-Fong Wei , Chia-Chen Lu , Chang-Chieh Chen , Hung-Chi Lin , David M. Ojcius4,5*, Hsin-Chih Lai2,5* 1 Department of Life Sciences, National Central University, Taoyuan, Taiwan, Republic of China, 2 Department of Medical Biotechnology and Laboratory Sciences, Chang Gung University, Taoyuan, Taiwan, Republic of China, 3 Department of Respiratory Therapy, Fu Jen Catholic University, Taipei, Taiwan, Republic of China, 4 Health Sciences Research Institute and School of Natural Sciences, University of California Merced, Merced, California, United States of America, 5 Center for Molecular and Clinical Immunology, Chang Gung University, Taoyuan, Taiwan, Republic of China 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. Ta