Tumor regression by phenethyl isothiocyanate involves DDB2

Nilotpal Roy1, Indira Elangovan, Dragana Kopanja

  • 1Department of Biochemistry and Molecular Genetics, Cancer Center, University of Illinois at Chicago, Chicago, IL, USA.

Cancer Biology & Therapy
|November 2, 2012
PubMed

Insights

Phenethyl isothiocyanate (PEITC) boosts the DNA repair protein DDB2, crucial for its tumor-suppressing effects. DDB2-deficient tumors do not respond to PEITC, highlighting DDB2

Area of Science:

  • Molecular Oncology
  • Cancer Chemoprevention
  • DNA Repair Mechanisms

Background:

  • Phenethyl isothiocyanate (PEITC), found in cruciferous vegetables, shows promise as a cancer chemopreventive and therapeutic agent.
  • DDB2 (damaged DNA binding protein 2) is a DNA repair protein involved in apoptosis and senescence, with attenuated expression in various cancers, including colon cancer.
  • The precise mechanism by which PEITC exerts its tumor-suppressive effects requires further elucidation.

Purpose of the Study:

  • To investigate the role of DDB2 in the tumor suppressive effects of PEITC.
  • To determine the molecular pathways involved in PEITC-induced DDB2 expression.
  • To assess the efficacy of PEITC in tumors with varying DDB2 expression levels.

Main Methods:

  • Treatment of colon cancer cells with PEITC.
  • Analysis of DDB2 expression and its regulation via reactive oxygen species and the p38MAPK/JNK pathway.
  • Evaluation of tumor progression in DDB2-deficient versus DDB2-proficient colon cancer models treated with PEITC.

Main Results:

  • PEITC treatment significantly increases DDB2 expression in colon cancer cells.
  • PEITC-induced reactive oxygen species augment DDB2 expression through the p38MAPK/JNK pathway, independent of p53.
  • DDB2-deficient colon cancer tumors are refractory to PEITC, exhibiting deficiencies in apoptosis and senescence, while DDB2-proficient tumors respond effectively.

Conclusions:

  • PEITC's tumor suppressive activity is critically dependent on its ability to induce DDB2 expression.
  • DDB2 induction by PEITC is mediated by reactive oxygen species and the p38MAPK/JNK pathway.
  • DDB2 expression is essential for PEITC's therapeutic efficacy in inhibiting colon cancer progression.

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