Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
10765381 | Biochemical and Biophysical Research Communications | 2010 | 5 Pages |
Abstract
Antibodies against the COOH-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-α, 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-α treatment prevented down regulation of ERK1/2 activation by either antibody or doxorubicin. Likewise, PFT-α prevented increases in the pro-apoptotic proteins BAD, BAK, BAX, PUMA, and NOXA as well as activation of caspases-3, -7, and -9. We conclude that antibody-induced apoptosis in prostate cancer cells is mediated predominantly by p53 using the mitochondrial pathway of apoptosis.
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Authors
U.K. Misra, S.V. Pizzo,