Implication of c-Myc in apoptosis induced by the retinoid CD437 in human lung carcinoma cells.
The novel synthetic retinoid 6-[3-(1-adamantyl)-4-hydroxyphenyl]-2-naphthalene carboxylic acid (CD437) has been recently identified to be a potent inducer of apoptosis in human non-small cell lung carcinoma (NSCLC) cells through a nuclear retinoic acid receptor independent mechanism. To approach the mechanism by which CD437 induces apoptosis in NSCLC cells, we investigated the involvement of c-Myc in CD437-induced apoptosis. CD437 (1 microM) up-regulated the expression of c-Myc and of its downstream target genes ornithine decarboxylase (ODC) and cdc25A in all three NSCLC cell lines (i.e., H460, SK-MES-1 and H1792) used. These effects were correlated with cellular susceptibilities to induction of apoptosis by CD437. Furthermore, CD437-induced apoptosis could be blocked by the ODC inhibitor difluoromethylornithine, the caspase inhibitors Z-VAD FMK and Z-DEVD FMK, and c-Myc antisense oligodeoxynucleotide, respectively. These data indicate that c-Myc gene plays an important role in mediating CD437-induced apoptosis in human NSCLC cells.
Sun
S Y
SY
Department of Thoracic/Head and Neck Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston 77030, USA.
Yue
P
P
Shroot
B
B
Hong
W K
WK
Lotan
R
R
D000590:Amino Acid Chloromethyl Ketones / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D002289:Carcinoma, Non-Small-Cell Lung / Q000473:pathology*; D003546:Cysteine Endopeptidases / Q000502:physiology; D015853:Cysteine Proteinase Inhibitors / Q000494:pharmacology; D000518:Eflornithine / Q000494:pharmacology; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D016259:Genes, myc; D006801:Humans; D008175:Lung Neoplasms / Q000473:pathology*; D016376:Oligonucleotides, Antisense / Q000494:pharmacology; D009842:Oligopeptides / Q000494:pharmacology; D009955:Ornithine Decarboxylase / Q000502:physiology; D065108:Ornithine Decarboxylase Inhibitors; D017027:Protein Tyrosine Phosphatases / Q000096:biosynthesis / Q000235:genetics; D016271:Proto-Oncogene Proteins c-myc / Q000502:physiology*; D012176:Retinoids / Q000494:pharmacology*; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000473:pathology; D020687:cdc25 Phosphatases
D000590:Amino Acid Chloromethyl Ketones; C099555:CD 437; D015853:Cysteine Proteinase Inhibitors; D016376:Oligonucleotides, Antisense; D009842:Oligopeptides; D065108:Ornithine Decarboxylase Inhibitors; D016271:Proto-Oncogene Proteins c-myc; D012176:Retinoids; C110772:benzoylcarbonyl-aspartyl-glutamyl-valyl-aspartyl-fluoromethyl ketone; C096713:benzyloxycarbonylvalyl-alanyl-aspartyl fluoromethyl ketone; C517004:CDC25A protein, human; D017027:Protein Tyrosine Phosphatases; D020687:cdc25 Phosphatases; D003546:Cysteine Endopeptidases; D009955:Ornithine Decarboxylase; D000518:Eflornithine