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.