Induction of apoptosis by phenethyl isothiocyanate in cells overexpressing Bcl-XL

• Published in: Cancer letters 2008-11, Vol.271 (2), p.215-221
• Main Authors: Cuddihy, Sarah L, Brown, Kristin K, Thomson, Susan J, Hampton, Mark B
• Format: Article
• Language: English
• Subjects: Anticarcinogenic Agents - pharmacology; Apoptosis; Apoptosis - drug effects; bcl-X Protein - genetics; bcl-X Protein - metabolism; Cancer; Cloning; Experiments; Flow cytometry; Hematology, Oncology and Palliative Medicine; Humans; Isothiocyanates - pharmacology; Jurkat Cells; Lymphoma; Medical research; Mutation; Phosphorylation; Proteins; Software; Studies
• ISSN: 0304-3835; 1872-7980
• DOI: 10.1016/j.canlet.2008.06.002

Abstract Isothiocyanates are a class of phytochemicals able to induce apoptosis in numerous cells including Jurkat T-lymphoma cells overexpressing the oncoprotein Bcl-2. To test if isothiocyanates are also effective against other anti-apoptotic members of the Bcl-2 family we generated Jurkat cells stably overexpressing Bcl-XL . Phenethyl isothiocyanate (PEITC) was cytotoxic to these cells, with an LD50 ranging from 9 to 18 μM depending on the level of Bcl-XL expression. Apoptosis induction in response to PEITC was confirmed by caspase activation and phosphatidylserine exposure. Isothiocyanates specifically target cysteine residues, therefore we tested the hypothesis that PEITC directly impairs Bcl-2 and Bcl-XL activity by interacting with their conserved cysteine residues. Jurkat cells overexpressing double cysteine mutants of Bcl-2 were generated, but they remained sensitive to PEITC. We conclude that PEITC antagonizes the action of anti-apoptotic Bcl-2 family members via an indirect mechanism.