Sodium orthovanadate inhibits p53-mediated apoptosis

Akinori Morita, Shinichi Yamamoto, Bing Wang, Kaoru Tanaka, Norio Suzuki, Shin Aoki, Azusa Ito, Tomohisa Nanao, Soichiro Ohya, Minako Yoshino, Jin Zhu, Atsushi Enomoto, Yoshihisa Matsumoto, Osamu Funatsu, Yoshio Hosoi, Masahiko Ikekita

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37 Citations (Scopus)

Abstract

Sodium orthovanadate (vanadate) inhibits the DNA-binding activity of p53, but its precise effects on p53 function have not been examined. Here, we show that vanadate exerts a potent antiapoptotic activity through both transcription-dependent and transcription-independent mechanisms relative to other p53 inhibitors, including pifithrin (PFT) α. We compared the effects of vanadate to PFTα and PFTμ, an inhibitor of transcriptionindependent apoptosis by p53. Vanadate suppressed p53-associated apoptotic events at the mitochondria, including the loss of mitochondrial membrane potential, the conformational change of Bax and Bak, the mitochondrial translocation of p53, and the interaction of p53 with Bcl-2. Similarly, vanadate suppressed the apoptosis-inducing activity of a mitochondrially targeted temperature-sensitive p53 in stable transfectants of SaOS-2 cells. In radioprotection assays, which rely on p53, vanadate completely protected mice from a sublethal dose of 8 Gy and partially from a lethal dose of 12 Gy. Together, our findings indicated that vanadate effectively suppresses p53-mediated apoptosis by both transcription-dependent and transcriptionindependent pathways, and suggested that both pathways must be inhibited to completely block p53-mediated apoptosis.

Original languageEnglish
Pages (from-to)257-265
Number of pages9
JournalCancer Research
Volume70
Issue number1
DOIs
Publication statusPublished - 2010 Jan 1
Externally publishedYes

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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  • Cite this

    Morita, A., Yamamoto, S., Wang, B., Tanaka, K., Suzuki, N., Aoki, S., Ito, A., Nanao, T., Ohya, S., Yoshino, M., Zhu, J., Enomoto, A., Matsumoto, Y., Funatsu, O., Hosoi, Y., & Ikekita, M. (2010). Sodium orthovanadate inhibits p53-mediated apoptosis. Cancer Research, 70(1), 257-265. https://doi.org/10.1158/0008-5472.CAN-08-3771