Pifithrin-α promotes p53-mediated apoptosis in JB6 cells

Akira Kaji, Yiguo Zhang, Masaaki Nomura, Ann M. Bode, Wei-Ya Ma, Qing Bai She, Zigang Dong

Research output: Contribution to journalArticle

28 Scopus citations

Abstract

Recently, blockage of p53-dependent transcriptional activation and apoptosis by pifithrin-α (PFTα) 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 PFTα 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 PFTα itself but were also enhanced by a combination of PFTα with UVB or Dox. Furthermore, PFTα-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 PFTα. Thus, we conclude that PFTα is not a specific p53 inhibitor in JB6 cells but is a potential activator of p53-mediated signaling and apoptosis.

Original languageEnglish (US)
Pages (from-to)138-148
Number of pages11
JournalMolecular Carcinogenesis
Volume37
Issue number3
DOIs
StatePublished - Jul 1 2003

Keywords

  • Apoptosis
  • Doxorubicin
  • ERKs
  • JNKs
  • MAPKs
  • P38 kinase
  • P53
  • Pifithrin-α (PFTα)
  • UV

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    Kaji, A., Zhang, Y., Nomura, M., Bode, A. M., Ma, W-Y., She, Q. B., & Dong, Z. (2003). Pifithrin-α promotes p53-mediated apoptosis in JB6 cells. Molecular Carcinogenesis, 37(3), 138-148. https://doi.org/10.1002/mc.10130