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Dietary phenethyl isothiocyanate alters gene expression in human breast cancer cells
Young Jin Moon1, Daniel A Brazeau, Marilyn E Morris
1Department of Pharmaceutical Sciences, School of Pharmacy and Pharmaceutical Sciences, University at Buffalo, State University of New York, Amherst, NY 14260, USA.
Abstract:
Phenethyl isothiocyanate (PEITC), a component in cruciferous vegetables, can block chemical carcinogenesis in animal models. Our objective was to determine the effect of treatment with PEITC on gene expression changes in MCF-7 human breast cancer cells in order to evaluate potential mechanisms involved in its chemopreventive effects. MCF-7 cells were treated for 48 hours with either PEITC (3 μM) or the vehicle. Total RNA was extracted from cell membrane preparations, and labeled cDNA's representing the mRNA pool were reverse-transcribed directly from total RNA isolated for use in the microarray hybridizations. Two specific human GE Array Kits (Superarray Inc.) that both contain 23 marker genes, related to signal transduction pathways or cancer/tumor suppression, plus 2 housekeeping genes (β-actin and GAPDH), were utilized. Arrays from treated and control cells (n = 4 per group) were evaluated using a Student's t-test. Gene expression was significantly induced for tumor protein p53 (p53), cyclin-dependent kinase inhibitor 1C (p57 Kip2), breast cancer Type 2 early onset (BRCA2), cAMP responsive element binding protein 2 (ATF-2), interleukin 2 (IL-2), heat shock 27 KD protein (hsp27), and CYP19 (aromatase). Induction of p57 Kip2, p53, BRCA2, IL-2, and ATF-2 would be expected to decrease cellular proliferation and increase tumor suppression and/or apoptosis. PEITC treatment produced significant alterations in some genes involved in tumor suppression and cellular proliferation/apoptosis that may be important in explaining the chemopreventive effects of PEITC.
Insights
Phenethyl isothiocyanate (PEITC) alters gene expression in breast cancer cells, potentially explaining its cancer-blocking effects. This study identified key genes involved in tumor suppression and cell proliferation affected by PEITC treatment.
Area of Science:
- Molecular Biology
- Cancer Research
- Biochemistry
Background:
- Phenethyl isothiocyanate (PEITC), found in cruciferous vegetables, exhibits chemopreventive properties demonstrated in animal models.
- Understanding the molecular mechanisms of PEITC's chemopreventive effects is crucial for its therapeutic application.
- MCF-7 human breast cancer cells provide a relevant model for studying PEITC's impact on cancer-related gene expression.
Purpose of the Study:
- To investigate the effects of PEITC on gene expression profiles in MCF-7 human breast cancer cells.
- To identify specific genes and pathways modulated by PEITC that contribute to its chemopreventive potential.
- To elucidate the molecular mechanisms underlying PEITC's anti-cancer activity.
Main Methods:
- MCF-7 cells were treated with PEITC (3 μM) or vehicle for 48 hours.
- Total RNA was extracted for microarray analysis using human GE Array Kits focusing on signal transduction and cancer/tumor suppression genes.
- Gene expression data from treated and control groups (n=4 per group) were analyzed using a Student's t-test.
Main Results:
- PEITC treatment significantly induced the expression of several key genes: tumor protein p53 (p53), cyclin-dependent kinase inhibitor 1C (p57 Kip2), breast cancer Type 2 early onset (BRCA2), cAMP responsive element binding protein 2 (ATF-2), interleukin 2 (IL-2), heat shock 27 KD protein (hsp27), and CYP19 (aromatase).
- Upregulation of p57 Kip2, p53, BRCA2, IL-2, and ATF-2 suggests potential roles in decreasing cellular proliferation and enhancing tumor suppression or apoptosis.
- Significant alterations in genes related to tumor suppression and cellular proliferation/apoptosis were observed.
Conclusions:
- PEITC significantly impacts the expression of genes involved in critical cellular processes relevant to cancer.
- The observed gene expression changes, particularly the induction of tumor suppressor and apoptosis-related genes, provide a molecular basis for PEITC's chemopreventive effects.
- Further research into these specific gene alterations may reveal novel therapeutic strategies utilizing PEITC for breast cancer prevention or treatment.
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