화학공학소재연구정보센터
Biochemical and Biophysical Research Communications, Vol.391, No.1, 272-276, 2010
PFT-alpha inhibits antibody-induced activation of p53 and pro-apoptotic signaling in 1-LN prostate cancer cells
Antibodies against the COCH-terminal domain of cell surface GRP78 induce apoptosis in cancer cell lines via activation of p53 signaling. We now have studied the effects of PFT-alpha, an inhibitor of p53-mediated apoptotic pathways, on anti-GRP78 antibody-induced activation of p53 and pro-apoptotic signaling in 1-LN prostate cancer cells Pretreatment of 1-LN cancer cells with this agent significantly inhibited antibody or doxorubicin-induced Upregulation of p53 Concomitantly, PFT-alpha, treatment prevented down regulation of ERK1/2 activation by either antibody or doxorubicin Likewise, PFT-alpha prevented increases in the proapoptotic proteins BAD, BAK, BAX, PUMA. and NOXA as well as activation of caspases-3, -7, and -9. We conclude that anti body-induced apoptosis in prostate cancer cells is mediated predominantly by p53 using the mitochondrial pathway of apoptosis. (c) 2009 Elsevier Inc. All rights reserved.