2004年9月
C-terminal peptides of p53 molecules enhance radiation-induced apoptosis in human mutant p53 cancer cells
APOPTOSIS
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- 巻
- 9
- 号
- 5
- 開始ページ
- 591
- 終了ページ
- 597
- 記述言語
- 英語
- 掲載種別
- DOI
- 10.1023/B:APPT.0000038044.40337.35
- 出版者・発行元
- KLUWER ACADEMIC PUBL
We propose here a novel p53-targeting radio-cancer therapy using p53 C-terminal peptides for patients having mutated p53. Hoechst 33342 staining showed that X-ray irradiation alone efficiently induced apoptotic bodies in wild-type p53 (wtp53) human head and neck cancer cells transfected with a neo control vector (SAS/neo cells), but hardly induced apoptotic bodies in mutation-type p53 (mp53) cells transfected with a vector carrying the mp53 gene (SAS/mp53). In contrast, transfection of p53 C-terminal peptides (amino acid residues 361-382 or 353-374) via liposomes caused a remarkable increase of apoptotic bodies in X-ray-irradiated SAS/mp53 cells, but did not enhance apoptotic bodies in X-ray-irradiated SAS/neo cells. In immunocytochemical analysis, positively stained cells for active type caspase-3 were observed at high frequency after X-ray irradiation in the SAS/mp53 cells pretreated with p53 C-terminal peptides. In SAS/neo cells, positively stained cells for active type caspase-3 were observed with X-ray irradiation alone. Furthermore, protein extracts from X-ray-irradiated SAS/mp53 cells showed higher DNA-binding activity of p53 to p53 consensus sequence when supplemented in vitro with p53 C-terminal peptides than extracts from non-irradiated SAS/mp53 cells. These results suggest that radiation treatment in the presence of p53 C-terminal peptides is more effective for inducing p53-mediated apoptosis than radiation treatment alone or p53 C-terminal peptide treatment alone, especially in mp53 cancer cells. This novel tool for enhancement of apoptosis induction in mp53 cells might be useful for p53-targeted radio-cancer therapy.
- リンク情報
- ID情報
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- DOI : 10.1023/B:APPT.0000038044.40337.35
- ISSN : 1360-8185
- Web of Science ID : WOS:000223332900009