Abstract
In the United States prostate cancer is the most commonly diagnosed cancer and is the second leading cause of death from malignancies in men. Dietary components have been recently targeted in the prevention and treatment of cancer, in combination with existing medical treatments for prostate cancer. Lycopene is a fat soluble red-orange carotenoid primarily consumed in foods containing tomatoes and tomato-derived products including tomato sauce, tomato paste and ketchup, with relatively smaller amounts in dried apricots, watermelon and pink grapefruit. Our objective is to determine whether lycopene treatment modulates prostate cancer biomarker genes in hormone-refractory human prostate cancer (PC-3) cell lines using Oligo GEArray® DNA Microarray which contains 263 genes involved in the prognosis and diagnosis of prostate cancer. Cell viability experiments determined that 25µM lycopene was the highest non-toxic treatment dose and therefore was selected for further experiments. Microarray image analysis demonstrated a decrease in the expression of transforming growth factor beta-2 (TGFβ-2), cyclin dependent kinase-9 (CDK-9), epidermal growth factor receptor (EGFR), B-cell lymphoma-2 (BCL-2), B-cell lymphoma-2 like 1 (BCL2L1), insulin-like growth factor 1 receptor (IGF1R), cyclin dependent kinase-7 (CDK-7), and breast cancer 1 (BRCA1) genes after the treatment of PC-3 cells with 25µM lycopene. Percent down-regulation calculated for TGFβ-2, CDK-9, EGFR, BCL-2, BCL2L1, IGF1R, CDK-7, and BRCA1 genes was 79%, 68%, 59%, 54%, 52%, 48%, 43%, and 38%, respectively, in lycopene-treated versus untreated samples. The modulated expressions of EGFR, IGF1R, BRCA1, CDK-9, TGFβ-2, CDK-7, and BCL-2 genes were validated using Real-Time Polymerase Chain Reaction (Real-Time PCR) and the results demonstarted a down-regulation of 72%, 61%, 56%, 56%, 44%, 34%, and 30%, respectively. Among all modulated prostate cancer biomarker genes, EGFR demonstrated the most consistent down-regulation in expression in our microarray and Real-Time PCR analyses. Protein expression analysis demonstrated that lycopene treatment also decreased EGFR protein expression in lycopene-treated PC-3 cells by 36%. These results indicate that the treatment of PC-3 cells with lycopene consistently modulates several prostate cancer biomarker genes. The present study clearly indicates that EGFR is down-regulated at the mRNA and protein levels after treatment with 25µM lycopene. Therefore, the results suggest that lycopene may be beneficial in delaying or preventing the progression of prostate disease.
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