Effect of beta-carotene-rich tomato lycopene beta-cyclase ( tlcy-b) on cell growth inhibition in HT-29 colon adenocarcinoma cells.
Lycopene beta-cyclase (tlcy-b) tomatoes, obtained by modulating carotenogenesis via genetic engineering, contain a large amount of beta-carotene, as clearly visible by their intense orange colour. In the present study we have subjected tlcy-b tomatoes to an in vitro simulated digestion and analysed the effects of digestate on cell proliferation. To this aim we used HT-29 human colon adenocarcinoma cells, grown in monolayers, as a model. Digested tomatoes were diluted (20 ml, 50 ml and 100 ml/l) in culture medium and added to the cells for different incubation times (24 h, 48 h and 72 h). Inhibition of cell growth by tomato digestate was dose-dependent and resulted from an arrest of cell cycle progression at the G0/G1 and G2/M phase and by apoptosis induction. A down-regulation of cyclin D1, Bcl-2 and Bcl-xl expression was observed. We also found that heat treatment of samples before digestion enhanced beta-carotene release and therefore cell growth inhibition. To induce with purified beta-carotene solubilised in tetrahydrofuran the same cell growth inhibition obtained with the tomato digestate, a higher amount of the carotenoid was necessary, suggesting that beta-carotene micellarised during digestion is utilised more efficiently by the cells, but also that other tomato molecules, reasonably made available during digestion, may be present and cooperate with beta-carotene in promoting cell growth arrest.
Palozza
Paola
P
Institute of General Pathology, Catholic University School of Medicine, largo F. Vito, Roma, Italy.
Bellovino
Diana
D
Simone
Rossella
R
Boninsegna
Alma
A
Cellini
Francesco
F
Monastra
Giovanni
G
Gaetani
Sancia
S
D000230:Adenocarcinoma / Q000188:drug therapy* / Q000473:pathology; D000704:Analysis of Variance; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D015415:Biomarkers / Q000032:analysis; D053148:Caspase 3 / Q000032:analysis; D003110:Colonic Neoplasms / Q000188:drug therapy* / Q000473:pathology; D019938:Cyclin D1 / Q000235:genetics; D004063:Digestion / Q000502:physiology; D015536:Down-Regulation; D019254:Genes, bcl-2; D005819:Genetic Markers; D019073:HT29 Cells; D006801:Humans; D007399:Interphase / Q000187:drug effects; D019753:Intramolecular Lyases / Q000627:therapeutic use*; D018551:Solanum lycopersicum / Q000201:enzymology* / Q000235:genetics; D030821:Plants, Genetically Modified; D013552:Swine; D051020:bcl-X Protein / Q000235:genetics; D019207:beta Carotene / Q000032:analysis / Q000627:therapeutic use*
D015415:Biomarkers; D005819:Genetic Markers; D051020:bcl-X Protein; D019207:beta Carotene; D019938:Cyclin D1; D053148:Caspase 3; D019753:Intramolecular Lyases; C070925:lycopene cyclase-isomerase