LYCOPENE AND ADVANCED PROSTATE CANCER
2003 BJU INTERNATIONAL
of the prostate cancer cell, and genetherapy.Among the many carotenoids lycopene hasbeen of special interest and has recentlyreceived attention because of suggestiveassociations in reducing the risk of cancer atmany sites, including breast, prostate andpancreas. Lycopene is one of the majorcarotenoids in the diet and accounts for abouthalf the carotenoids in human serum. Theanticancer action of this carotenoid canbe explained by several mechanisms; (i)inhibition of cell proliferation ; (ii)induction of cell differentiation andapoptosis; (iii) antioxidant, singlet-oxygenquencher and protection against oxidativeDNA damage [3–7]; (iv) potentiation of theimmune system; and (v) stimulation of gap junction communication . Throughthese mechanisms lycopene controls cellproliferation and facilitates tumourregression.Epidemiological data suggest that theenvironment is responsible for most prostatecancers. One major mechanism by which theenvironment can inﬂuence carcinogenesis isoxidative damage, i.e. the generation of reactive oxygen species that act as freeradicals and damage important biomolecules,including DNA, proteins and lipids. Anantioxidant is deﬁned as any compoundwhich breaks the free-radical reaction chain.Tomatoes are the primary dietary source of lycopene, which is one of the most potentantioxidants among the carotenoids [9–12].Many experimental studies also support theview that oxidative damage is associated withprostate cancer. There is an associationbetween prostate cancer and dietary fatconsumption (a major substrate for oxidativestress), and oxidative biomarker data suggestincreased oxidative stress among patientswith prostate cancer. There are ubiquitousdefects in the glutathione-s-transferase-
pathway (a major endogenous antioxidantmechanism), and evidence that androgens (animportant promoter of prostate cancergrowth) work in part by generating reactiveoxygen species.In a recent study, Chen
 examinedthe effects of lycopene on oxidative DNAdamage and PSA levels in patients withlocalized prostate cancer. Thirty-two patientsconsumed tomato sauce-based pasta dishesfor the 3 weeks (30 mg of lycopene per day)before their scheduled radical prostatectomy.Serum PSA levels decreased after theintervention, from 10.9 to 8.7 ng/mL, i.e. by17.5% (
< 0.001). In a similar study, Kucuk
 obtained a PSA decrease of 18% afteradministering 15 mg of lycopene twice dailyfor 3 weeks, whereas it increased by 14% inthe control group (
0.25). In the presentstudy the decrease in PSA level was alsogreater in the OL group (Table 1) at 6 months.These changes were more consistent at2 years (
< 0.01). The reasons for thisconsistent and more durable decrease in PSAlevel in the OL group can be attributed tolycopene-induced protective mechanisms, e.g.possible escape from the usual hormone-independent state at 1.5–3 years,antiproliferative activity, normalization of celldifferentiation and regulation of apoptosis.Besides being an antioxidant and singletoxygen quencher, lycopene also inhibits cellproliferation, and induces cell differentiationand apoptosis . Pastori
 reportedthat simultaneous addition of lycopene and
-tocopherol, at physiological concentrations(< 1 and 50
mol/L, respectively) resulted instrong inhibition of prostate cancer cellproliferation of up to 90%. Kotake-Nara
 assessed the effects of 15 kinds of carotenoids on the viability of three lines of human prostate cancer cells, PC-3, DU 145and LNCaP. Acyclic carotenoids such asphytoﬂuene, zeta-carotene and lycopene, allof which are present in tomato, signiﬁcantlyinhibited cell proliferation and reduced cellviability. Logically this antiproliferative andinhibitory effect should act on the primarymalignancy and metastasis, helping to reducethe gland and the secondaries. Kucuk
 conducted a randomized trial of 26 menwith newly diagnosed, clinically localized(14 T1 and 12 T2) prostate cancer (15 mgof lycopene twice daily, 15 men, or nosupplementation, 11 men) for 3 weeks beforeradical prostatectomy. Eleven men in thelycopene group and two in the control grouphad no involvement of surgical margins and/or extraprostatic tissues by cancer (
0.02).Twelve men in the lycopene and ﬁve in thecontrol group had tumours of <4 mL(
0.22). This suggests that the process of malignant transformation declined and thetumour regressed. The present data also showsimilar beneﬁcial changes on bone scans, withtwice the rate of CR (regression of bonesecondaries) in the OL than in the controlgroup. Similarly, there was greater diseaseprogression in the control group at 6 months,and a greater improvement in peak ﬂow rateand other voiding symptoms secondary to thereduction of the malignant gland, furthersupporting the anticancer properties of lycopene. Lycopene has also shown adramatic response in hormone-resistantprostate cancer, opening a new possibletreatment for such difﬁcult patients .There was a longer overall survival in the OLgroup (
< 0.01) than after orchidectomyalone, but it is too early to be sure that thesurvival beneﬁt would be statisticallysigniﬁcant in the long-term. Appropriatelong-term randomized studies are requiredto provide further evidence to theseobservations.
Kotake-Nara E, Kushiro M, Zhang H,Sugawara T, Miyashita K, Nagao A.
Carotenoids affect proliferation of humanprostate cancer cells.
Anticancer Res Apr
Djuric Z, Powell LC.
Antioxidant capacityof lycopene-containing foods.
Int J Food Sci Nutr
Matos HR, Capelozzi VL, Gomes OF,Mascio PD, Medeiros MH.
Lycopeneinhibits DNA damage and liver necrosis in
The Kaplan-Meier curve for the duration of survival in the OL group (red line) and control (greendashed line).
% p a t i e n t s a l i v e