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Introduction

Prostate cancer is the most common malignant disease of urology and also the

most common noncutaneous malignancy in males. Globally, there were estimated

782,600 new cases and 254,000 cancer deaths in 2007.1 Furthermore, data from

Global Estimates of Cancer (GLOBOCAN) 2008, showed the incidence of

prostate cancer was 27.9 per 100,000 and ranked second after lung cancer.2 From

1960s to 2002, there is a trend of the prostate cancer percentage increasing in

Asian countries (low risk areas), such as in Japan (6.5 times) and Singapore (4

times), compared with Scandinavian countries and the United States .3,4 Incidence

of prostate cancer in various Asian countries increases with a range of 5 ̶ 118% . 5

The incidence of prostate cancer in China is 1.7 per 100,000 person / year and in

India 4.6 per 100,000 person / year. 4 The incidence of prostate cancer in Indonesia

is not known for certain, roughly 4.5 ̶ 9.8 per 100,000 population in 2002 and

increased to 7.5 ̶ 14 per 100,000 in 2008.6,7 Sugandi's research8, found in 10 years

(from 1976 ̶ 1985) of 211 cases of malignancy that came to RSUP Hasan Sadikin

Bandung, 13% (47 cases) is prostate cancer. The Safriadi9 study shows prostat

cancer case is increase in 2004-2011 periode of prostate cancer at. kasus kanker

prostat ini meningkat pada periode tahun 2004-2011 amounting to 375 cases.

Until now, the exact cause of prostate cancer is not yet known, however, some

reports suggest that there are several risk factors for prostate cancer like

environment and genetic. For example, Japanese and Chinese who have long lived

in the United States, have a higher risk of contracting and dying of prostate cancer
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than their siblings who still living in the country of origin, yet the incidence of

prostate cancer in Asian races living in the United States is lower than the white

race and African race living in the United States. This suggests that genetic factors

play a role as a risk for prostate cancer.10

Another factor that plays an important role in the occurrence of prostate cancer

is nutrition. Tambunan and Umbas11, reported that nutrients that have protective

effects against risk and prostate cancer are tomato / lycopene, soy, cruciferous

vegetables, green tea, and other polyphenolic compounds.

In the course of prostate cancer who get hormonal therapy, most cases will

experience resistance to hormonal therapy. This is called castration resistance

prostate cancer and eventually the patient dies

Many epidemiological studies by observing community groups with low

incidence of malignancy to is conducted to reduce the risk of prostate cancer..

Vecchia13, Rao14 and Basu15 conducted several case-control studies in the period

1983 ̶ 1992, found that in Mediterranean communities, who consumed many fruits

and vegetables including tomatoes, had a low incidence of malignancy. A case-

control study in Minnesota found that people who consumed tomatoes more than

14 times per month had a lower risk of prostate cancer than those who ate

tomatoes less than 3 times per month.16

. Tomato and its products are the main source of lycopene. Lycopene is a 40-

carbon acyclic carotenoid containing 11 conjugated double bonds and belongs to a

subgroup of carotenes comprising only hydrogen and carbon atoms.17,18

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Research about the effects of tomatoes on the risk of prostate cancer still

continues, however the results of the study, there is some supporting results and

some are not supporting the effects of tomatoes. Several studies that supported

includes Mills et al19 in the 1970s, conducted a 6-year cohort study of 14,000

Seventh-day adventist men and found that men who consumed more than 5

servings of tomatoes and their products each week, has a lower risk of prostate

cancer than men who eat less than one serving of tomatoes or a product every

week.20

In the Health Professional Follow-up Study (HPFS) report of 47,000 health

workers in 1995, it was found that among the fruits that could potentially decrease

the incidence of prostate cancer were raw tomatoes and strawberries. 20 Etminan et

al.21 conducted a meta-analysis to the role of tomatoes in cancer prevention

prostate. The results are the consumption of raw tomatoes reduce the incidence of

prostate cancer with a relative risk of 0.89.

Some studies in mice about the effects of tomatoes on prostate cancer include

Siler et al.22 reported that lycopene increases the rate of necrosis. This corresponds

to the decrease in local androgen regulatory signals and the expression of IGF-1

and interleukin 6 (IL-6) in MatLyLu Dunning prostate cancer model (30 male

Copenhagen mice). Tang et al.23 found that lycopene inhibited the growth of

prostate cancer cells in vitro in male BALB / c nude mice.

Research on humans reported by Obermuller-Jevic et al.24 found that

lycopene inhibited the growth of normal human prostate epithelial cells in vitro

(Prec-clone 6448). Kucuk dkk.25 found that lycopene administration in 26

prostate
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cancer patients before radical prostatectomy reduced the surgical incision and

extension of extraprostatic tumors and decreased diffuse pattern of High grade

prostatic intraepithelial neoplasm (HGPIN). Ansari and Gupta26 studied lycopene

administration in 20 prostate cancer patients who had been refractory to androgens

and found 5% of patients had a complete response of normal prostate specific

antigen (PSA) and no signs of illness for 8 weeks. Furthermore, 35% of patients

had PSA regression, 50% of patients with stable PSA levels, and only 15%

experienced progression.

Some of the mechanisms of lycopene in inhibiting prostate cancer

progression have been recognized, among others, as antioxidants, cell progression

inhibitors, apoptotic induction, and insulin growth factor type 1 (IGF-1) insulin

growth inhibitors. 15,17,26,27

As an antioxidant, lycopene works by capturing nonradical and radical

molecules such as singlet oxygen, then discharged in the form of heat energy or

motion. In addition, lycopene also captures free radical molecules such as oxygen

radicals that then free radicals are destroyed.28

As a cell cycle progression inhibitor, lycopene halts progression of human

prostate cancer cell line LNCaP and PC3 in G0 / G1 phase by decreasing levels of

cyclin D1 and E and cyclin dependent kinase.28

. The process of tumor cell apoptosis can occur through intrinsic or extrinsic

pathways. Lycopene stimulates apoptosis through intrinsic pathways, by

stimulating the proapoptotic factor of the mitochondrial cavity such as the Bax /

Bak protein (an apoptotic promotor) by decreasing the transmembrane potential of

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the mitochondria thus inducing the release of cytochrome c into the cytoplasm.

Furthermore, it interacts with APAF-1 and cysteine-aspartic proteases 9 (caspase-

9) which stimulates caspase-3 resulting in apoptosis. There are two types of

caspase namely caspase initiator and caspase effector. Caspase initiator (caspase-

2, -8, -9, -10) activates the inactive form of caspase effector. Caspase effector

(caspase-3, -6, -7) activates a particular protein in the cell, which further

stimulates apoptosis. In addition, lycopene also induces proapoptotic Bax

cytokines.29 Lycopene does not work on extrinsic paths.29

Lycopene inhibits DHT signal transduction which further inhibits IGF-1

expression. Lycopene also increases the effect of serine phosphorylation on Akt

and GSK3β and tyrosine phosphorylation on GSK3, which in turn inhibits cell

growth.30