Benzyl isothiocyanate modulated apoptotic genes in breast cancer cell lines Free

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The incidence, mortality rates and outcomes of treatment of breast cancer within different populations are modified by the myriad of internal and external influences of which dietary compounds are included. Benzyl isothiocyanate (BITC), a cruciferous vegetable-derived compound, has been shown to inhibit chemically induced cancer in animal models. Moreover, epidemiological studies have provided compelling evidence to suggest that cruciferous vegetables may reduce cancer risk.
 >The aim of this study was to compare the proliferation and diverse gene expression in African American (MDA-MB-468) and Caucasian cell lines (MDA-MB-231) after exposure to BITC. MTT was also used to examine the inhibitory effects of BITC to the breast cancer cell lines. BITC significantly inhibited proliferation of human breast cancer cells in a concentration-and time dependent manner with an IC(50) of approximately 8uM. Antiproliferative effect of BITC was stronger in African American than Caucasian cell lines.
 >We investigated the expression profiles of genes involved in apoptosis pathway in the two breast cancer cell lines by using a human RT² Profiler PCR Array (SuperArray) spotted with 84 genes relevant to apoptosis. Although it has been previously demonstrated that isothiocyanates induce cell death, the mechanism of such cell death in different breast cancer cell lines was not well established. The mRNA extracted from these specimens was transcribed into cDNA and analyzed with RT² Profiler PCR Arrays specific to Human Apoptosis pathways.
 >In comparison to the untreated controls, BITC administration upregulated 45 genes in MDA-MB-231 at least 2-fold; whereas, 79 genes were over expressed and 21 genes were down regulated in MDA-MB-468 cells. BCL-2 family, Death Domain Family, Death Effector Domain Family and P53 and DNA Damage Response genes were significantly upregulated in MDA-MB-468 cell lines. The analysis of apoptotic gene expression pattern through the use of PCR microarray technology suggested that BITC could induce different pathways and molecules in African American and Caucasian breast cancer cell lines.
 >In the present study, we investigated the mechanism by which BITC induced anti-proliferative activity in human breast cancer cell lines. We also described the molecular pathways underlying BITC-induced apoptosis in breast cancer cell lines. This data may be helpful to identify the intracellular targets of BITC, a compound with a potential use as a chemopreventive/ therapeutic target against breast cancer.