CDDP induces p53-dependent apoptosis in tongue cancer cells.
We have investigated the CDDP sensitivities of two tongue cancer cell lines with differing p53 genetic status, one with wild-type p53 (SAS) and the other with mutant-type p53 (HSC-4). SAS was about 2 times more sensitive at the D10 dose and demonstrated increased p53 and Bax protein levels at 10 h after CDDP treatment on Western blot analysis. On the other hand, overexpression of p53 in HSC-4 was observed without CDDP treatment and no elevation of Bax could be detected. Apoptosis was observed after CDDP treatment in SAS but not in HSC-4 by Hoechst 33342-staining and electrophoresis methods. These findings indicate that p53 plays an important role in apoptosis as a positive regulator of Bax expression. It is suggested that p53 status may have predictive potential with regard to response to CDDP therapy.
Department of Otorhinolaryngology, NARA Medical University, Kashihara, Nara, Japan. jibika@nmu-gw.naramed-u.ac.jp
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Kanata
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Yane
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Ota
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Miyahara
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Matsunaga
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Takahashi
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Ohnishi
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Ohnishi
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Hosoi
D017209:Apoptosis / Q000187:drug effects*; D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000473:pathology*; D002945:Cisplatin / Q000494:pharmacology*; D004273:DNA, Neoplasm / Q000235:genetics; D019008:Drug Resistance, Neoplasm; D016158:Genes, p53; D006801:Humans; D009363:Neoplasm Proteins / Q000096:biosynthesis / Q000502:physiology*; D016133:Polymerase Chain Reaction; D018807:Polymorphism, Single-Stranded Conformational; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis; D019253:Proto-Oncogene Proteins c-bcl-2; D014062:Tongue Neoplasms / Q000235:genetics / Q000473:pathology*; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000473:pathology; D016159:Tumor Suppressor Protein p53 / Q000096:biosynthesis / Q000502:physiology*; D051028:bcl-2-Associated X Protein
C494826:BAX protein, human; D004273:DNA, Neoplasm; D009363:Neoplasm Proteins; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D016159:Tumor Suppressor Protein p53; D051028:bcl-2-Associated X Protein; D002945:Cisplatin