Effects of Lycopene on Protein Expression in Human Primary Prostatic Epithelial Cells

Abstract

Clinical trials and animal studies have suggested that lycopene, the red carotenoid found in tomatoes, might be useful for the prevention of prostate cancer in the diet or as a dietary supplement through a variety of chemoprevention mechanisms. Since most mechanism of action studies have used prostate cancer cells or involved men with existing prostate cancer, we investigated the effects of lycopene on protein expression in human primary prostatic epithelial cells. After treatment with lycopene at a physiologically relevant concentration (2 μM) or placebo for 48 h, the primary prostatic epithelial cells were lysed and fractionated using centrifugation into cytosolic/membrane and nuclear fractions. Proteins from lycopene-treated and placebo-treated cells were trypsinized and derivatized for quantitative proteomics using isobaric tags for relative and absolute quantitation (iTRAQ) reagent. Peptides were analyzed using 2-dimensional microcapillary HPLC-tandom mass spectrometry to identify proteins that were significantly up-regulated or down-regulated following lycopene exposure. Proteins that were most affected by lycopene were those involved in antioxidant responses, cytoprotection, apoptosis, growth inhibition, androgen receptor signaling, and the Akt/mTOR cascade. These data are consistent with previous studies suggesting that lycopene can prevent cancer in human prostatic epithelial cells at the stages of cancer initiation, promotion and/or progression.

Dietary Tomato and Lycopene Impact Androgen Signaling- and Carcinogenesis-Related Gene Expression during Early TRAMP Prostate Carcinogenesis

“…Previously, tomato and lycopene were reported to inhibit prostatic steroid binding protein mRNA expression, AR coregulator (Protein DJ1), and an androgen receptor-stabilizing chaperone protein (HSP90) in the prostate of healthy rats, the Dunning rat model, and human primary prostate epithelial cells (9, 10, 39). That Pxn is impacted by tomato and lycopene is a novel finding.…”

A multi-targeted approach to suppress tumor-promoting inflammation

“…Lycopene has been found to increase the effects of deoxification proteins (such as epoxide hydrolase-1) and protective enzymes (such as glutathione- S -transferase-omega-1, peroxiredoxin-1 and sulphide-quinone oxidoreductase) [486]. Other studies have shown that lycopene downregulates the genes that regulate proteins involved in the generation of ROS, including ERO1-like protein-a and CLIC-1 [487]. In addition, lycopene may prevent cancers, especially prostate cancer, via other mechanisms.…”

Investigation of the Potential Anticancer Effects of Lycopene in Tissue Engineered In vitro and In vivo Models

“…Lycopene levels were evaluated from venous blood samples using highpressure liquid chromatography. However, this study also comprised a high risk of bias due to measurement of only one blood sample per patient [51]. A meta-analysis of three prospective and seven case-control studies concluded an inverse association between the consumption of dietary lycopene and the risk of developing ovarian cancer.…”

“…Jeong et al [51] reported a 90 % reduction of ovarian cancer risk related to lycopene consumption, assessed in a Korean hospital-based case-control study, which included 45 patients with epithelial ovarian cancer and 135 cancer-free controls. Lycopene levels were evaluated from venous blood samples using highpressure liquid chromatography.…”

“…Teodoro et al [72] found increased apoptosis rates in DU145 prostate cancer cells after incubation with 3 µM lycopene for 96 h. This dose comes close to those found in humans [72]. In a proteomic study using primary prostatic epithelial cells instead of a prostate cancer cell line, treated with 2 µmol/L of a lycopene beadlet formulation for 48 h, Qiu et al investigated lycopene-induced changes in the expression profile of proteins, thereby finding an upregulation of pro-apoptotic proteins (tyrosyl-tRNA synthetase, 40S ribosomal protein S3 and pyruvate kinase isozyme M2), as well as a downregulation of anti-apoptotic proteins (chloride intracellular channel protein 1, heat shock 70 kDa protein 1A/B, HSPβ1, Rho GDP-dissociation inhibitor 1, translationally controlled tumour protein, lactoylglutathione lyase, 78 kDa glucose-regulated protein and protein-kinase C inhibitor protein1) [51]. However, irrespective of changes in protein levels, there was no evidence of apoptosis in lycopene-treated primary prostatic epithelial cell cultures [51].…”