@article{oai:repo.qst.go.jp:00045712,
 author = {Morita, Akinori and Yamamoto, Shinichi and Bing, Wang and Tanaka, Kaoru and Suzuki, Norio and Aoki, Shin and Ito, Azusa and Nanao, Tomohisa and Ohya, Souichirou and Zhu, Jin and Yoshino, Minako and Enomoto, Atsushi and Matsumoto, Yoshihisa and Funatsu, Osamu and Hosoi, Yoshio and Ikekita, Masahiko and 王 冰 and 田中 薫},
 issue = {1},
 journal = {Cancer Research},
 month = {Jan},
 note = {We recently reported a novel suppressive effect of sodium orthovanadate (vanadate) on the DNA-binding activity of p53. Here, we showed that vanadate had a more potent antiapoptotic activity than three other chemical p53 inhibitors, including pifithrin-alpha. Although the other agents inhibited p53's transcriptional activity, they did not suppress p53-dependent apoptosis in irradiated MOLT-4 cells. To investigate the cause for the different effects of vanadate and the other inhibitors, we chose PFT-alpha and PFT-mu (an inhibitor of the p53-mediated transcription-independent apoptotic pathway), as references, and determined their and vanadate's effect on p53-mediated apoptosis, with a focus on the transcription-independent pathway. We found that vanadate suppressed the 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 p53's interaction with Bcl-2. Vanadate also suppressed the apoptosis-inducing activity of a mitochondrially targeted temperature-sensitive p53 in stable transfectants of the SaOS-2 cell line. Finally, we tested vanadate's potential as a radioprotector. Vanadate completely protected mice from a sublethal dose of 8 Gy and partially from a lethal dose of 12 Gy. Our data demonstrate that vanadate can suppress both the transcription-dependent and the transcription-independent p53 pathways, and suggest that both pathways must be inhibited to completely block p53-mediated apoptosis.},
 pages = {257--265},
 title = {Sodium orthovanadate inhibits p53-mediated apoptosis},
 volume = {70},
 year = {2010}
}