Table 2.

Main findings of the effect of tomato compounds on cancers.

Biological Property Studied	Type of Study (In Vitro/In Vivo)	Main Findings	References
Antioxidant and anticancer activity	In vitro study with human prostate cancer (PC-3) and human breast adenocarcinoma (MCF-7) cell lines.	Cell viability assay showed chemically induced lycopene oxidised products (1–50 µM) were a key component in cancer cell apoptosis.	[152]
	In vitro study with HL-60 human promyelocytic leukaemia cells.	Products of lycopene oxidation, identified by spectral analyses, were added to HL-60 cell suspension as a 1% (v/v) concentration. This treatment was shown to induce apoptosis in leukaemia cells, shown using flow cytometry to evaluate the ratio of apoptotic cell death.	[151]
Anti-angiogenic role in cancer cells	In vitro study testing human umbilical vein endothelial cells (HUVEC) and rat aortic rings.	Lycopene inhibited angiogenesis in HUVEC and rat aortic rings at physiologically relevant concentrations (1–2 μmol/L) when angiogenesis was analysed using phase-contrast microscopy.	[159]
	In vitro and in vivo study testing human umbilical vein endothelial cells (HUVEC).	Lycopene (0, 1, 5, 10 µM) was shown to inhibit angiogenesis of HUVEC cells in vitro and in vivo by inhibiting MMP-2/uPA system through VEGFR2-mediated PI3K–Akt and ERK/p38 signalling pathways. Cell proliferation assessed using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay, cell migration assessed with Millipore QCM™ Endothelial Migration Assay Kit.	[168]
	Longitudinal cohort study.	Lycopene used as a marker of tomato intake and higher intake inversely correlated with total, and the aggressive nature of prostate cancer. The reduced severity of cancer and lesser degree of angiogenesis were reported only in individuals who consumed a tomato-rich diet for a long time period but not in those whose intake recently increased. Tissue microarrays and immunohistochemistry were used to assess tumour biomarker expression.	[169]
Modulation of molecular pathways in cancer cells	In vitro study with HT-29 human colon cancer cells.	Lycopene treatment (0, 2, 5, 10 µM) was shown to inhibit the PI3K–AKT signalling pathway in colon cancer cells, demonstrating its effects on tumour development via angiogenesis inhibition. Assessment of cell proliferation using MTT assay and gene expression investigated using transient transfection and luciferase reporter assays.	[157]
	Ex vivo and in vivo study testing human umbilical vein endothelial cells (HUVEC) and rat aortic rings.	Lycopene (400 μg/mouse) reduced angiogenesis cell signalling through inhibition of the VEGF cell signalling pathway. Anti-angiogenic activity of lycopene confirmed by ex vivo rat aortic ring and in vivo chorioallantoic membrane assays.	[167]
	In vitro study with human prostate (PC-3) and breast (MDA-MB-231) cancer cell lines.	Lycopene (0.5–5 µM) inhibited different stages of the NF-κB cell signalling pathway in both cancer cell lines in vitro as seen in Western blots and NF-κB-responsive gene activation reporter assays.	[77]
	In vitro study in human gastric cancer (AGS) cells.	Lycopene at 0.3% was shown to induce apoptosis by inhibiting Wnt/β-catenin signalling, stopping the nuclear translocation of β-catenin and suppressing the expression of specific cell survival genes AGS cells. Cell viability, DNA fragmentation, and ROS concentrations were examined in these cells.	[150]
Cytotoxicity and cancer cell growth	In vitro study testing human prostate epithelial cells (PrEC).	PrEC treated with lycopene (up to 5 μmol/L) showed no expression of cyclin D1 in vitro. This regulatory subunit of kinases essential to the cancer cell cycle, resulting in reduced cancer cell cycle progression. High-performance liquid chromatography (HPLC) analysis, a thymidine incorporation assay, and flow cytometry were carried out to assess the impact of lycopene.	[199]
	In vitro study testing human prostate (PC-3) and breast (MDA-MB-231) cancer cell lines.	PC-3 and MDA-MB-231 cancer cell lines were tested in vitro in the absence and presence of lycopene at concentrations of 0.5–5 µM. MTS cell growth assays, Western blots, and NF-κB-responsive gene activation reporter assays showed that lycopene inhibits the NF-kB pathway at different stages in both cell lines.	[77]
	In vitro study treating Caco-2 colon cancer cells.	Treatment of Caco-2 colon cancer cells with 150 μmol/L dietary fibre ferulic acid delayed cell cycle progression in the S phase. Gene expression was analysed with cDNA microarray technique.	[115]
Cancer cell apoptosis	In vitro study testing human prostate cells (PC-3).	Flow cytometry analysis showed 27–32% apoptosis in PC-3 when supplemented with (10–50 μM) β-carotene.	[174]
Gap junction communication in cancer cells	In vitro study with rat liver epithelial WB-F344 cells.	Incubation of WB-F344 cells with oxidation products of lycopene (0.2% v/v) improved the gap junction communication in dye transfer assay using microinjection of the fluorescent dye Lucifer Yellow CH.	[203]