LYCOPENE- ITS ROLE, MECHANISM AND EFFECT IN PCa
A number of systematic reviews on before and after, case–control, cohort and RCTs have been performed—all with varying conclusions about the efficacy of lycopene in the prevention of prostate disease. A systematic review reporting the results of five before and after studies on lycopene for the prevention and treatment of prostate disease identified that three out of the five studies reported a significant decrease in prostate-specific antigen (PSA) levels post-intervention. Only one of the before and after studies reported a significant reduction in Lycopene for the Prevention and Treatment of Prostate Disease 111 pain—with the same study reporting a significant improvement in LUTS. A systematic review of observational studies identified 11 case–control and 10 cohort studies investigating lycopene as a preventive agent for prostate disease. Pooled analysis of the case–control and cohort studies demonstrated little benefit from lycopene supplementation in the prevention of prostate cancer. However, a pooled analysis of all observational studies identified in that systematic review suggests a potential benefit in the consumption of high concentrations of lycopene for potentially preventing prostate cancer. Systematic reviews of RCTs in 2011 and 2012 identified eight RCTs that have investigated the merits of lycopene in the prevention and treatment of BPH and/or prostate cancer. Meta-analysis of two studies identified a significant decrease in PSA levels in men allocated to receive lycopene Mean difference (MD) = -1.58 (95 %CI -2.61, -0.55) (Ilic and Misso 2012). Further meta-analysis of two studies within the review identified no significant reduction in the incidence of BPH (RR = 0.92 (95 %CI 0.66, 1.29)) or prostate cancer diagnosis (RR = 0.95 (95 %CI 0.63, 1.44)) between men receiving lycopene supplementation or placebo. No adverse events were reported across the systematic reviews regarding ingestion of lycopene.
Lycopene is a bright red carotenoid (a carotenoid without Vitamin A activity) hydrocarbon found in tomatoes and other red fruits and vegetables, such as red carrots, watermelons, grapefruits, and papayas with sufficient and ample antioxidant and anti-cancer properties. Lycopene has been linked to many other health benefits which ranges from heart health to protection against sunburns and so on. The health related effects were known from early 1990s. Test-tube studies which lasted till 2016 as per those early data showed that the nutrient may slow down the growth of breast and prostate cancers by limiting tumour growth. This 23-year study in more than 46,000 men carefully examined the link between lycopene and prostate cancer in more detail. And they found that men who consumed at least two servings of lycopene-rich tomato sauce per week were 30% less likely to develop prostate cancer than those who ate less than one serving of tomato sauce per month [10]
Another double-blind placebo-controlled study concluded that after 28 days of using lycopene juices, the concentration of lycopene in serum increased to 80.2 % which was higher when compared with the placebo. This result leads to a conclusion that lycopene reduces DNA damages, oxidative stress, and risk of disease [11]. The analytical results of a study men population who were newly diagnosed with prostate cancer who received lycopene twice a day for 3 weeks, showed that lycopene effectively decreases the risk and growth of prostate cancer cells.
Lycopene’s ability to prevent cancer is mediated by a number of direct mechanisms, including signal regulation, cell cycle arrest, induction of apoptosis, and changes in enzymes and antioxidants, all of which prevent cancer cells from spreading, invading, and angiogenesis[12-14]. Lycopene decreases or suppresses the carcinogenic effects of Rb (retinoblastoma protein) and p53 (tumour protein p53) proteins on phosphorylation, and arrests the cell cycle by inhibiting the expression of cyclin D1 in the G0/G1 phases, according to new research [15]. Lycopene has been shown to inhibit the growth of normal human PrEC (prostate epithelial cells) in cell culture medium and to affect the cell junction between cancer cells in in vitro studies [15]. Higher serum levels of IGF-1 (Insulin-Like Growth Factor 1) are linked to prostate and breast cancer, and lycopene can slow cell cycle progression by interfering with IGF-1 mitogenic pathways [16, 17]. Lycopene has been shown to regulate the differentiation of intrathymic T cells, which can suppress tumour cell development in SHN virgin mice models[18]. Lycopene inhibited the phosphorylation of GSK-3 (glycogen synthase kinase-3), AKT, and ERK1/2 (extracellular signal-regulated protein kinases 1 and2), which interfered with PI3K (phosphatidylinositol-3-kinase)/AKT and MAPK (mitogen-activated protein kinase)/ERK signalling pathways in in-vitro studies on HT-29 cells (human colon cancer cell line). Lycopene also resulted in significant reduction of nuclear proteins such as AP-1 (Activator protein-1) and beta-catenin [19]. Lycopene inhibited cell proliferation and induction of apoptosis in PC3 cells by lowering the expression of AKT2 and increasing the expression of miR let-7f1 (mi-croRNA Lethal-7) [20]. Evaluations of the effects of lycopene and beta-carotene on AtT20 cells (Musmusculus pituitary tumour) have shown a negative relation to regulating the aggressive form of AtT20 cells. These substances can lower the expression of ACTH (Adrenocorticotropic hormone) and Skp2 (S-phase kinase-associated protein2) while increasing the expression of p27kip1 (Cyclin-dependent kinase inhibitor) and phosphorylated connexin 43. Lycopene can block the inter-cellular gap junction communications and thus regulate cancer progression [21, 22] as these Gap Junction communication of cancer cells are responsible for invasion and allows a metastatic type of cancer.