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Mol Carcinog. 2003 Jul;37(3):138-48.

Pifithrin-alpha promotes p53-mediated apoptosis in JB6 cells.

Author information

1
Hormel Institute, University of Minnesota, Austin, Minnesota 55912, USA.

Abstract

Recently, blockage of p53-dependent transcriptional activation and apoptosis by pifithrin-alpha (PFTalpha) has been reported to be useful for reducing the side effects of cancer therapy and the compound is thus thought to be a specific inhibitor of p53 [Komarov et al., Science 1999;285:1733-1737]. Here, we found that PFTalpha did not inhibit UVB- or doxorubicin (Dox)-stimulated p53-mediated transcriptional activation and apoptosis in JB6 cells. Instead, p53-dependent activation and apoptosis were not only induced by PFTalpha itself but were also enhanced by a combination of PFTalpha with UVB or Dox. Furthermore, PFTalpha-induced apoptosis was mediated through p53-dependent and -independent signaling pathways. Extracellular signal-regulated kinases and p38 kinase, but not c-jun N-terminal kinases (JNKs), were activated, and these activations were required for phosphorylation and accumulation of p53 in the cellular apoptotic response to PFTalpha. Thus, we conclude that PFTalpha is not a specific p53 inhibitor in JB6 cells but is a potential activator of p53-mediated signaling and apoptosis.

PMID:
12884365
DOI:
10.1002/mc.10130
[Indexed for MEDLINE]

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