Trimidox-induced apoptosis is mediated through induction of p53 in NALM-6 cells.
We examined the effect of trimidox-induced apoptosis involvement of p53 in the NALM-6 cell line of acute lymphoblastic leukemia. Trimidox has been shown to increase the induction of p53. Phosphorylation of p53 protein at Ser-15 and Ser-20 residues was activated earlier than the obvious increase in p53 expression. Pifithrin-alpha, a p53 inhibitor, significantly prevented trimidox-induced apoptotic characteristics, as detected by nuclear morphological observation and DNA fragmentation. Trimidox-induced apoptosis was enhanced or attenuated by transfection with wild-type or dominant-negative p53 containing expression vectors, respectively. These results indicate that one of the induction mechanisms of apoptosis by trimidox is the mediated augmentation of p53.
Kanno
Syu-Ichi
S
Department of Clinical Pharmacotherapeutics, Tohoku Pharmaceutical University, Japan. syu-kan@tohoku-pharm.ac.jp
Ohtake
Takaharu
T
Osanai
Yuu
Y
Kurauchi
Kaori
K
Ujibe
Mayuko
M
Uwai
Koji
K
Takeshita
Mituhiro
M
Satoh
Susumu
S
Ishikawa
Masaaki
M
D017209:Apoptosis / Q000187:drug effects*; D001550:Benzamidines / Q000494:pharmacology*; D045744:Cell Line, Tumor; D053938:DNA Fragmentation; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D006801:Humans; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy* / Q000473:pathology; D012264:Ribonucleotide Reductases / Q000037:antagonists & inhibitors*; D015398:Signal Transduction; D016159:Tumor Suppressor Protein p53 / Q000502:physiology*
C074761:3,4,5-trihydroxybenzamidoxime; D001550:Benzamidines; D004791:Enzyme Inhibitors; D016159:Tumor Suppressor Protein p53; D012264:Ribonucleotide Reductases