Diallyl Sulfide inhibits Diethystilbestrol induced Breast Tumor in Female ACI rats
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Previous studies in this lab have shown that diallyl sulfide (DAS) inhibits DNA adduct formation, lipid peroxidation and modulate detoxification and DNA repair genes and enzymes in breast tissue of diethylstilbesterol (DES) treated female ACI rats. These findings are important since estrogen and estrogenic compounds such as DES have been shown to induce breast cancer in humans and animals. In addition, scientists have postulated that DAS, a constituent of garlic, is an effective cancer prevention agent. In this study, we hypothesize that the release of inteleukin 6 by DES induced cancerous cells leads to activation of the JAK Stat pathway which can increase cell proliferation and inhibit apoptosis. DAS may modulate these changes. To prove this hypothesis, 6 week old female ACI rats were implanted with Control (silicon implant alone) and DES (50mg/kg) silicon pellets were implanted s.c. In addition, these animals were fed normal chow or DAS (as cotreatment) containing chow ad libitum for six months. At sacrifice, representative mammary tissueand all palpable mammary tumors were removed for genetic and histopathologicalanalysis. Genetic analysis was done by microarray analysis and validated using PCR array. Our data show significant increase in interleukin 6 gene expression in cancerous cells (DES group) and a significant decrease in the DAS cotreatment group. Furthermore, a significant modulation of genes associated with the JAK/STAT pathway was observed. Animals cotreated with DAS were free of tumor. For the first time our lab was able to show that DAS prevents DES induced breast tumors in female ACI rats.Funded by RCMI Grant #2G12RR0302024
