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

Sarah L Cuddihy1, Kristin K Brown, Susan J Thomson

  • 1Free Radical Research Group, Department of Pathology, University of Otago, PO Box 4345, Christchurch, New Zealand. sarah.cuddihy@otago.ac.nz

Cancer Letters
|July 22, 2008
PubMed

Insights

Phenethyl isothiocyanate (PEITC) induces apoptosis in cancer cells by indirectly targeting anti-apoptotic Bcl-2 family proteins. This phytochemical shows cytotoxicity against Jurkat cells overexpressing Bcl-X(L).

Area of Science:

  • Biochemistry
  • Molecular Biology
  • Cancer Research

Background:

  • Isothiocyanates are phytochemicals known to induce apoptosis, programmed cell death, in various cancer cells.
  • The Bcl-2 family of proteins, including Bcl-2 and Bcl-X(L), are key regulators of apoptosis, often overexpressed in cancer to promote cell survival.
  • Previous studies show isothiocyanates are effective against Jurkat T-lymphoma cells overexpressing Bcl-2.

Purpose of the Study:

  • To investigate the efficacy of isothiocyanates, specifically phenethyl isothiocyanate (PEITC), against other anti-apoptotic members of the Bcl-2 family.
  • To determine if PEITC directly interacts with conserved cysteine residues in Bcl-2 and Bcl-X(L) to impair their function.
  • To elucidate the mechanism by which PEITC antagonizes anti-apoptotic Bcl-2 family members.

Main Methods:

  • Generation of Jurkat cells stably overexpressing Bcl-X(L).
  • Assessment of PEITC cytotoxicity using LD(50) determination.
  • Confirmation of apoptosis induction via caspase activation and phosphatidylserine exposure assays.
  • Creation and testing of Jurkat cells overexpressing double cysteine mutants of Bcl-2.

Main Results:

  • PEITC demonstrated cytotoxicity against Jurkat cells overexpressing Bcl-X(L), with LD(50) values ranging from 9 to 18 microM.
  • Apoptosis induction by PEITC was confirmed through caspase activation and phosphatidylserine exposure.
  • Jurkat cells overexpressing Bcl-2 cysteine mutants remained sensitive to PEITC, indicating no direct interaction with these residues.

Conclusions:

  • PEITC effectively induces apoptosis in cancer cells expressing anti-apoptotic Bcl-2 family proteins like Bcl-X(L).
  • The mechanism of PEITC's action against Bcl-2 family proteins is indirect, not involving direct interaction with their conserved cysteine residues.
  • PEITC represents a potential therapeutic agent for cancers characterized by the overexpression of anti-apoptotic Bcl-2 family members.

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