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Published on: August 1, 2025
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.
Abstract:
Phenethyl isothiocyanate (PEITC) is a promising cancer chemopreventive agent commonly found in edible cruciferous vegetables. It has been implicated also for therapy, and is in clinical trial for lung cancer. Here, we provide evidence that the tumor suppressive effect of PEITC is related to its ability to induce expression of damaged DNA binding protein 2 (DDB2), a DNA repair protein involved also in apoptosis and premature senescence. DDB2 expression is attenuated in a wide variety of cancers including the aggressive colon cancers. We show that, in colon cancer cells, reactive oxygen species, which are induced by PEITC, augment expression of DDB2 through the p38MAPK/JNK pathway, independently of p53. PEITC-induced expression of DDB2 is critical for inhibition of tumor progression by PEITC. Tumors derived from DDB2-deficient colon cancer cells are refractory to PEITC-treatments, resulting from deficiencies in apoptosis and senescence. The DDB2-proficient tumors, on the other hand, respond effectively to PEITC. The results show that PEITC can be used to induce expression of DDB2, and that expression of DDB2 is critical for effective response of tumors to PEITC.
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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