Induction of apoptosis by phenethyl isothiocyanate in cells overexpressing Bcl-XL.
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-X(L). Phenethyl isothiocyanate (PEITC) was cytotoxic to these cells, with an LD(50) ranging from 9 to 18 microM depending on the level of Bcl-X(L) 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-X(L) 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.
Cuddihy
Sarah L
SL
Free Radical Research Group, Department of Pathology, University of Otago, PO Box 4345, Christchurch, New Zealand. sarah.cuddihy@otago.ac.nz
Brown
Kristin K
KK
Thomson
Susan J
SJ
Hampton
Mark B
MB
D016588:Anticarcinogenic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D006801:Humans; D017879:Isothiocyanates / Q000494:pharmacology*; D019169:Jurkat Cells; D009154:Mutation; D051020:bcl-X Protein / Q000235:genetics / Q000378:metabolism*
D016588:Anticarcinogenic Agents; D017879:Isothiocyanates; D051020:bcl-X Protein; C058305:phenethyl isothiocyanate