Lycopene is a well-known compound found commonly in tomatoes which brings wide range of health benefits against cardiovascular diseases and cancers. From an anti-cancer perspective, lycopene is often associated with reduced risk of prostate cancer and people often look for it as a dietary supplement which may help to prevent cancer.
Compound | Subject | Experiment Design | Outcome | Reference |
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Lycopene (Lyc) | SK-Hep-1 cells (highly invasive hepatoma cell line) | Treatment with 1, 2.5, 5, 10, 20 µmol/L Lyc | ↓cell migration, invasion (bell-shaped manner) ↑nm23-H1 (bell-shaped manner) nm23-H1 and cell migration and invasion (-ve r) |
[16] |
Treatment with 1–10 µM Lyc | ↓cell invasion, MMP-9, NF-κB, Sp1, IGF-1R, ROS | [17] | ||
Treatment with 1, 2.5, 5, 10 µM Apo-8′-lycopenal (Lyc metabolite), 10 µM Lyc | (Lyc, Apo-8′-lyc)↓cell invasion, migration (Apo-8′-lyc) ↓MMP-2, -9, Rho GTPase, ERK/p38, PI3K-Akt ↑nm23-H1, TIMP-1,-2 |
[18] | ||
Compound | Subject | Experiment Design | Outcome | Reference |
---|---|---|---|---|
Lycopene (Lyc) | High mammary tumor strain of SHN virgin mice | Control (1), 5 × 10−5% Lyc (2), AIN-76TM diet | ↓mammary tumor development, TYMS, serum FFA, prolactin | [67] |
Sprague Dawley rats | N-methylnitrosourea (intrarectal, 1 wk), followed by administration of Lyc (1), lutein (2), α-carotene (3), β-carotene (4), palm carotene (5), daily gavage (wk 2 and wk 5) | ↓aberrant crypt foci development | [77] | |
Male weanling rats | Induction of hepatocarcinogenesis by 6 × 100 mg/kg BW diethylnitrosamine (DEN)/100 mg/kg BW 2-nitropropane (2-NP), fed with 300 mg/kg β-carotene (1), canthaxanthin (2), astaxanthin (3), Lyc (4), 15,000 retinol equiv. excess vit A (5), 3-methycholanthrene (6) intraperitoneal, 3–4 wks | ↔No., size of preneoplastic liver foci ↓size of GGT+, GST+ foci, Liver volume fraction occupied by foci Note: modulate P-450 2E1, not antioxidant properties |
[70] | |
] | ||||
Hepatocellular carcinoma (HCC)LEC rats | Diet containing 0.005% Lyc (1), 1% TJ-9: crude extracts of 7 herbs (2), control (3) administered from 6 wks age to 76 wks age | ↔number, mean area and % area GST-P-+ focal lesions (liver, HCC); Note: TJ-9 had higher number of GST-P-+ lesion in HCC), AFP, cumulative survival rates ↓iron conc. in liver |
[81] | |
N-methyl-N’-nitrosoguanidine (MNNG) and saturated NaCl (S-NaCl) induced Male Wistar rats | N-methyl-N’-nitrosoguanidine (MNNG) + saturated NaCl (1), MNNG + S-NaCl + Lyc (2), Lyc (3), Control (4) | ↓gastric carcinomas ↑GSH, GPx, GST, GR |
[73] | |
MNNG + S-NaCl (1), MNNG + S-NaCl + Sallylcysteine (SAC) (2), MNNG + S-NaCl + Lyc (3), MNNG + S-NaCl + SAC + Lyc (4), chemoprevention agents (5–7), Control (8) |
Compound | Subject | Experiment Design | Outcome | Ref | ||||
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Lycopene (Lyc) | 47,894 human subjects initially free of diagnosed cancer | Validated semiquantitative food-frequency questionnaire | ↓risk of non-stage A1 prostate cancer | [83] | ||||
26 male patients with prostate cancer, 14 stage T1, 12 stage T2 | Control (1), 15 mg Lyc (2) | ↓plasma prostate-specific antigen (PSA) ↑connexin 43 ↔Bcl-2, Bax Note: sample size is relatively small |
[86] | |||||
47,365 participants | Dietary questionnaires | ↓risk of prostate cancer Note: moderate association |
[84] | |||||
Treatment with Lyc (0.1–5 µM), induced with TGF-β | ↓NOX4 mRNA, NOX, ROS, cell migration, invasion, adhesion activity, MMP-9, MMP-2 | [19] | ||||||
Multiorgan carcinogenesis B6C3F1 mice model | Combined treatment with diethylnitrosamine (DEN), N-methyl-N-nitrosourea (MNU) and 1,2-dimethylhydrazine (DMH), Lyc + water: 25/50 ppm (1), Control (2), Lyc only: 25/50 ppm (3), 21 wks | |||||||
32 patients with localized prostate adenocarcinoma | Randomized placebo-controlled study: 30 mg Lyc/day | ↓incidences and multiplicities of lung adenomas and carcinomas Note: restricted to male, G1 with 50ppm Lyc ↔aberrant crypt loci, tumors in colon and kidney among groups |
↑serum and prostate Lyc conc., apoptotic index (hyperplastic and neoplastic cells) ↓serum PSA, leukocyte 8OHdG[80] |
[87] | H-Ras MCF10A, MDA-MB231 (highly aggressive breast cancer cell) | Treatment with Lyc | ↓cell invasion, migration, proliferation ↓ERK, Akt |
[20] |
58,279 men aged 55–69 yrs: 642 prostate cancer cases | Cohort study, 6.3 yrs follow-up, semi-quantitative food-frequency questionnaire | ↔risk of prostate cancer | [96] | HT-29 cells (human colon cancer cells) | Treatment with Lyc | ↓cell invasion, MMP-7, phosphorylation of Akt, GSK-3β, ERK ½, AP-1, β-catenin ↑E-cadherin stabilization |
[21] | |
69 men with favourable risk prostate cancer | 3-month randomized, double blinded clinical trial: 30 mg/day Lyc (1), 3 g/day fish oil (2), placebo (3) | ↔IGF-1, COX-2 | [97] | ER/PR+ MCF-7, HER2+ SK-BR-3, MDA-MB-468 cell lines | Treatment with Lyc (168 h) | inhibition of cell cycle progression G0/G1 ↑PARP cleavage, ERK1/2, p21, Bax ↓cyclin D1, Akt, mTOR ↔Bcl-xL |
[23] | |
↔GSH (stomach, erythrocytes), GPx (liver, erythrocytes), GPx activities (stomach), Bax, Bim | ||||||||
11 cohort studies, 6 nested case–control studies | Meta-analysis | OR < 1 (high tomato intake and incidence of prostate cancer) Modest effect in prevention of prostate cancer |
[89] | HGC-27 cell lines | Incubated with various conc of Lyc for 24, 48 or 72 h | ↑LC3-I, p-ERK |
[63] | |
↑GSH (liver), GPx (stomach), GSH activities, GPx activities (liver, erythrocytes), caspase-8 | Balb/c nude mice model | Injected with HGC-27 cells, fed with 20, 30, 60 mg/kg Lyc per d, oral | ↓tumour weight | |||||
F344/NSlc rats | ||||||||
26 studies with 17,517 cases of prostate cancer, from 563,299 participants | ↓tumor burden, Bcl-2 | Meta-analysis[26] | Lymphocytes from human blood |
Incubation with 10, 20, 40 µM/mL Lyc, before and after X-irradiation at doses of 0.5, 1 and 2 Gy | ↓DNA damage Note: Lyc administration after irradiation, no effect | |||
↓risk of prostate cancer (Lyc: 9–21 mg/day; plasma Lyc: 2.17–85 µg/dL) | [ | 90 | ] | Resistant hepatocyte (RH) model of hepatocarcinogenesis Wistar rats | 70 mg/kg BW lutein (1), Lyc (2), Control (3) Note: Low doses are useful |
[64] | ||
↑liver carotenoid conc. | ↔incidence, total number, multiplicity of hepatocyte nodules ↓No., size, area of GST+ preneoplastic lesions, hepatic DNA strand breakage |
[71] | ||||||
Colon carcinogenesis Sprague Dawley rat model | Induction by azoxymethane, followed by treatment with diallylsulfide (1), Lyc (2), theaflavin (3) | ↓aberrant crypt foci, preneoplastic lesion, COX-2, iNOS | [60] | (Pancreatic cancer) PANC-1 cells | Treatment with 0.25, 0.5 µM for 24 h | ↓ROS, NF-κB, cIAP1, cIAP2, survivin ↑caspase-3, Bax:Bcl-2 |
[24] | |
Nude mice | Supplementation 2× per wk (12 wks), with 1, 20 mg/kg BW Lyc, 20 mg/kg BW β-carotene; starting wk 2, injection with SK-Hep-1 cells via tail vein | ↓MMP-2, VEGF, tumor metastasis, mean no. of tumors, tumor cross-sectional area, PCNA, MMP-9 ↑nm23-H1 |
[22]Mouse epidermal cell line, JBG P+ (JB6 Cl 41-5a) | Pretreatment with Lyc for 5 days, incubation with TPA, with or without Lyc for 14 days | ↓colony formation, (mRNA) KEAP1 ↑(mRNA) SOD1, GSR, GPX1, CAT, GCLC, GCLM, NQO-1, HMOX1, nuclear NRF2 localization, LC3, p62 |
[65] | ||
Mice | Subjected to DMBA (60 µg) dissolved in 0.2 mL topically on back, after 1 week, TPA (4 µg) twice a week for 32 weeks; Control group (1), 8 µmol Lyc/d since first week (2), 8 µmol Lyc/d from first wk to 4th week only (3), 8 µmol Lyc/d since fourth week (4), Acetone/d since fourth week (5): 32 weeks experiment | ↑survival rate, GSH/GSSG ratio, SOD, GR, GPx, CAT, (mRNA) SOD1, GSR, GPX1, CAT, GCLC, GCLM, NQO-1, HMOX1 Note: lycopene was more effective as a pretreatment and during promotion phase of induced tumors.NRF2 was required for the effect of lycopene-induced prevention against tumor |
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2 mg/ 4 mg N-methylnitrourea x 3 per wk (3 wks), plain water (1), 17 ppm Lyc (2), diluted tomato juice with 17 ppm Lyc (3), diluted tomato juice with 3.4 ppm Lyc (4) | Apo-10′-lycopenoic acid, A-10-LA (Lyc metabolite) | NHBE cells (human bronchial epithelial cells), BEAS-2B-immortalized normal bronchial epithelial cells, A549 (non-small cell lung cancer cells) | Treatment with apo-10′-lycopenoic acid | ↓cyclin E inhibition of cell cycle progression G(1)→S ↑p21, p27, RAR beta |
[14] | |||
A/J mouse model | NNK injection (induction) and supplemented (10, 40, 120 mg/kg of A-10-LA | ↓tumor multiplicity | ||||||
BEAS-2B cells | Treatment with apo-10′-lycopenoic acid | ↑NRF2, HO-1, NAD(P)H dehydrogenase (quinone 1), GSTs, GCL, GSH | [66] | |||||
(3) ↓colon cancer incidence, but not in (2) | [ | 78 | ↓incidence rate, multiplicity of cutaneous papillomas, increased in epidermal thickness, invasion of benign papillomas, 8-OHdG, 4HNE | Human liver THLE-2, HuH7 cells | Treatment with apo-10′-lycopenoic acid | ↑SIRT1, p21, apoptosis ↓cyclin D1 |
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C57BI/6J mice | Supplementation with A-10-LA (10 mg/kg) for 24 wks, high fat diet, induced with diethylnitrosamine | ↓tumor multiplicity, volume, incidence, caspase-1, TNF-α, IL-6, NF-κB p65, STAT3, Akt, cyclin D1 ↑SIRT1, PARP cleavage |
[25] | |||||
Apo-8′-lycopenal (Lyc metabolite) | Human HepG2 cells | Treatment with 1, 5, 10 µM Apo-8′-lycopenal (Lyc metabolite), 10 µM Lyc | ↓cell invasion, migration ↑NRF2, HO-1, NQO-1 ↓KEAP1 |
[15] |
Hepatocarcinogenesis in rat model | |||||||
Injected with diethylnitrosamine (DEN) and fed with control diet or high fat diet (HFD) with or without Lyc or tomato extract | |||||||
(HFD + Lyc) ↓no. of GST+ hepatic foci, PCNA, cyclin D1, ERKs, NF-κB | |||||||
↔TNF-α, IL-1β, IL-12, CYP2E1 | |||||||
↑HO-1, NRF2 | |||||||
[ | 72 | ] | |||||
N-methyl-N′-nitrosoguanidine (MNNG) gastric cancer rat model | Control (1), 200 mg/kg BW MNNG + saturated NaCl (2), 200 mg/kg BW MNNG + saturated NaCl + 50 mg/kg BW Lyc (3) 200 mg/kg BW MNNG + saturated NaCl + 100 mg/kg BW Lyc (4) 200 mg/kg BW MNNG + saturated NaCl + 150 mg/kg BW Lyc (5) | ↑SOD, CAT, GSH-Px, IL-2, IL-4, IL-10, TNF-α, IgG, IgA, IgM ↓MDA, IL-6 |
[61] | ||||
BCO2-knockout and wild-type male mice | Lyc supplementation (100 mg/kg diet, 24 wks), induced by high fat diet | (BCO2-KO) ↑hepatic Lyc, miR-199a/b, miR214 ↓hepatocellular carcinoma incidence, multiplicity, ER(UPR), Met mRNA, β-catenin, mTORC1 (Wild type) ↓NF-κB p65, STAT3, IL-6, inflammatory foci | |||||
18 prospective cohort studies in 2012 | Pooled analysis (interval collapsing method) | Protective effect towards ER−/PR+ or ER−/PR− breast cancer | [91] | ||||
Plasma Lycopene | 25,802 persons: 103 men with prostate cancer, 103 men as control | Analysis of serum | ↔risk of prostate cancer | [94] | |||
209 prostate cancer cases, 228 control, Black and white men in US (40–79 yrs old) | Analysis of serum carotenoids | ↔risk of prostate cancer, only useful particularly for aggressive disease Note: insignificant inverse association (serum Lyc and prostate cancer) |
[95] | ||||
450 incident prostate cancer cases | Case-control study nested within prospective Health Professionals Follow-up Study | ↓risk of prostate cancer Note: restricted to older participants, without family history |
[85] | ||||
521 women with breast cancer | Analysis of serum using HPLC | ↓risk of breast cancer among premenopausal women and all ER/PR subtypes | [92] | ||||
17 prospective studies with 3603 cases, 458,434 participants | Meta-analysis | Nonlinear dose-dependent (lung cancer and plasma Lyc) Note: stronger inverse association at low plasma Lyc conc.) | [62] | ||||
[ | 93 | ] | (In vitro) OV-MZ-6 cells | Treatment with 2, 5 µM Lyc | ↓ITGA5, pERK 1/2 ↔ITGB1, tERK, vimentin |
[75] | |
Lycopene-rich tomato | 79 prostate cancer patients | Nutritional intervention: tomato products with 30 mg Lyc (1), tomato products + selenium, omega-3 fatty acids, soy isoflavones, grape/pomegranate juice and green/black tea (2), Control (3) | ↓PSA level | [88 | (In vivo) Ovarian cancer-bearing mice | Prevention Gp: Placebo (1), Lyc (2) Treatment Gp: Placebo (1), Lyc (2), Lyc + Taxol (3), Taxol + Platin (4), Platin (5), Lyc + Taxol + Platin (6) Concentration of Lyc: 0.75 mg/mL |
(Lyc Prevention Gp) ↓metastatic load, Ki67, ITGA5B1, ITGA5, ILK, ITGB1, FAK, MMP-9, serum and ascites CA125, EMT markers in metastatic tissue (Note: MMP-9 restricted to metastatic tissue, not tumor tissue) ↔tumor load, serum and ascites MMP-9 (Lyc Treatment Gp) ↓tumor load, Ki67, ITGA5, ITGA5B1, ascites CA125 ↑MMP-9 ↔ILK, ITGB1, FAK, serum and ascites MMP-9, serum CA125 |
Laying hens | Control (1), 200 mg/kg per kg diet Lyc (2), 400 mg/kg per kg diet Lyc (3) | ↓incidence, no. and size ovarian tumor, rate of adenocarcinoma, MDA, NF-κB, STAT3 ↑NFE2, HO-1 |
[76] | ||||
] | (In vitro) Lewis lung carcinoma (LLC) cells | Control (1), Lyc: 10 µM (2), Lyc: 20 µM (3), Lyc: 40 µM (4) | ↑(mRNA) IFNβ, IFNγ, IRF1, IRF7, CXCL9, CXCL10, pJAK, pSTAT3 ↓(mRNA) DMNT3a, methylation levels of promoters (IRF1, IRF7), PD-1 due to IFNγ, pAkt ↔(mRNA) DNMT1, DNMT3b |
[69] | |||
(In vivo) C57BL/6 mice | Control (1), Anti PD-1, 6 mg/kg (2), Lyc, 40 mg/kg (3), Anti-PD-1 + Lyc (4); intraperitoneal, 3 days, 4 times | ↓tumor volume, weight, IL-4, IL-10, (mRNA) DMNT3a, methylation levels of promoters (IRF1, IRF7) ↑IL-2, IFNγ, CD4+:CD8+, % IFNγ+/CD8+ T cell, % perforin+/CD8+ T cell, % granzyme B+/CD8+ T cell, (mRNA) IFNβ, IFNγ, IRF1, IRF7, CXCL9, CXCL10 ↔(mRNA) IRF3, IRF8, DNMT1, DNMT3b |
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CD-1 mice in AOM-DSS model | Normal (1), AOM+DSS control (2), (Bifidobacterium longum) BF + AOM + DSS (3), BF + Lyc 20 mg/kg + AOM + DSS (4), BF + Lyc 50 mg/kg + AOM + DSS (5), Lyc 20 mg/kg + AOM + DSS (6), Lyc 50 mg/kg + AOM + DSS (7), Metformin + AOM + DSS (8) |
↑positive rates of IGF-1, IGF-2 (high dose), IGF-1R, IGF2BP1, IGFBP2 (low dose), IGFBP3 (high dose), lymphocyte infiltration ↓inflammation incidence, positive rates of IGF-2 (low dose), IGFBP2 (high dose), IGFBP3 (low dose) ↔No. of tumors, adenocarcinomas incidence Note: presence of focal necrosis |
[79] | ||||
Lycopene-Enriched Tomato Oleoresin (LETO) | Rat mammary tumor model | Induced with 7, 12-dimethyl-benz[a]anthracene (DMBA) 2 wks, followed by injection of 10mg/kg LETO (1), β-carotene (2), control (3) twice per wk, 16 wks | ↑plasma, hepatic Lyc ↓tumors, tumor area |
[68] | |||
Supplementation with 250 ppm Lyc (1), 500 ppm (2), 250 ppm lycopene-rich tomato carotenoid oleoresin (TCO) (3), 500 ppm TCO (4), control (5) followed by initiation with N-methylnitrosourea (NMU) (7 days) 18 wks experimentation | ↔tumor incidence, latency, multiplicity, volume, total tumors per group Note: supplementation with TCO ↑serum Lyc conc. > supplementation with pure Lyc |
[82] |