Lycopene modulates growth and survival associated genes in prostate cancer

Abstract

Lycopene is a fat soluble red-orange carotenoid pigment present in tomato that reduces the risk for prostate cancer, a common malignancy among men. However, the mechanism by which lycopene attenuates prostate cancer is not fully defined. In this study we examined the effect of lycopene on proliferation, survival, and biomarker gene expression in prostate cancer (PC-3) cells in culture. WST-1 assay showed that lycopene induces a biphasic effect on PC-3 cells with a modest increase in proliferation at 1-5 μM, no change at 10-25 μM and a decrease at 50-100 μM doses in culture. Interestingly, combination treatment with lycopene induced anti-proliferative effect of Temozolomide on PC-3 cells. Lycopene also augmented the anti-proliferative effect of peroxisome proliferator-activated receptor gamma (PPARγ) agonists, but not Doxorubicin or Taxol, in prostate cancer. Flow cytometry analyses showed that lycopene, in combination with chemotherapeutic agents and PPARγ agonists, induced modest cell cycle arrest with significant increase in cell death by apoptosis and necrosis on prostate cancer. Gene array and quantitative reverse transcription polymerase chain reaction analyses showed that lycopene alters the expression of growth and apoptosis associated biomarkers in PC-3 cells. These findings highlight that lycopene attenuates prostate cancer by modulating the expression of growth and survival associated genes.

Keywords: B-cell lymphoma-2 like 1; B-cell lymphoma–2; BCL-2; BCL2L1; BRCA1; CDK-7; CDK-9; Cancer prevention; Carotenoids; EGFR; FBS; IGF1R; Lycopene; PBS; PC-3 cells; Prostate cancer; Real-Time PCR; Real-Time polymerase chain reaction; TGFβ-2; Transforming growth factor beta-2; breast cancer 1; cyclin dependent kinase-7; cyclin dependent kinase–9; epidermal growth factor receptor; fetal bovine serum; insulin-like growth factor 1 receptor; phosphate-buffered saline.