P53 mediates ceramide-induced apoptosis in SKN-SH cells

• Published in: Oncogene Vol. 21; no. 13; pp. 2020 - 2028
• Main Authors: SUNG SU KIM, CHAE, Hee-Sun, BACH, Jae-Hyung, MYOUNG WOO LEE, KYUNG YONG KIM, WON BOK LEE, JUNG, Young-Min, BONVENTRE, Joseph V, SUH, Yoo-Hun
• Format: Journal Article
• Language: English
• Published: Basingstoke Nature Publishing 21.03.2002; Nature Publishing Group
• Subjects: Ageing, cell death; Antisense oligonucleotides; Apoptosis; Apoptosis - drug effects; Bcl-2 protein; bcl-2-Associated X Protein; Biological and medical sciences; Care and treatment; Caspase Inhibitors; Caspase-1; Caspase-3; Caspases - metabolism; Cell cycle; Cell death; Cell physiology; Cell transformation and carcinogenesis. Action of oncogenes and antioncogenes; Ceramide; Ceramides; Ceramides - pharmacology; DNA damage; Dose-Response Relationship, Drug; Enzyme Activation - drug effects; Enzyme Inhibitors - pharmacology; Fundamental and applied biological sciences. Psychology; Genetic aspects; Health aspects; Humans; Kinases; Molecular and cellular biology; Neuroblastoma; Neuroblastoma - genetics; Neuroblastoma - metabolism; Neuroblastoma - pathology; Oligonucleotides, Antisense; p53 Protein; Physiological aspects; Proteins; Proto-Oncogene Proteins - metabolism; Proto-Oncogene Proteins c-bcl-2 - metabolism; Time Factors; Tumor Cells, Cultured; Tumor suppressor genes; Tumor Suppressor Protein p53 - genetics; Tumor Suppressor Protein p53 - metabolism; South Korea; United States > US; Massachusetts; Signal transduction; Cell line; p53 Protein; Ceramide; Neuroblastoma; Onc gene; Apoptosis
• DOI: 10.1038/sj.onc.1205037
• ISSN: 0950-9232

Ceramide induces apoptotic cell death in a dose- and time-dependent manner in neuroblastoma SKN-SH cells. Pretreatment with caspase inhibitors blocks cell death, suggesting that a set of caspase activities including caspase 1, as well as caspase 3, are involved in ceramide-induced apoptosis in SKN-SH cells. Treatment with a caspase inhibitor 3 h after ceramide addition did not inhibit cell death, although caspase activity was substantially reduced. Ceramide-induced apoptosis is accompanied by accumulation of p53 followed by an increase of Bax and decrease of Bcl-2 levels. Inhibition of p53 expression with p53 antisense oligonucleotides inhibits apoptosis and prevents the increase in Bax and decrease in Bcl-2. Furthermore, pretreatment with p53 antisense oligonucleotides markedly inhibits the induction of caspase activity. These results suggest that p53 regulates the ratio Bcl-2/Bax and the expression/activation of caspases during ceramide-induced apoptosis in SKN-SH cells. Caspase inhibition did not alter the expression of p53, Bcl-2 and Bax. Thus ceramide-induced reduction in the Bcl-2/Bax ratio, increase in caspase activity, and apoptosis is dependent upon increases in cellular p53 levels which play a critical role in the regulation of apoptotic cell death.