News Article | May 15, 2017
A new study shows that whole tomato extracts from two different Southern Italy cultivars inhibit gastric cancer cell growth and malignant features, paving the way for future studies aimed at implementing lifestyle habits not only for prevention, but potentially as a support to conventional therapies. “Their antitumoral effect seem not related to specific components, such as lycopene, but rather suggest that tomatoes should be considered in their entirety,” says Daniela Barone, researcher at the Oncology Research Center of Mercogliano (CROM), and one of the authors of the study. Experiments analyzed whole tomato lipophilic extracts for their ability to tackle various neoplastic features of gastric cancer cell lines. Extracts of both the San Marzano and Corbarino tomato varieties were able to inhibit the growth and cloning behavior of malignant cells. Treatment with the whole tomato extracts affected key processes within the cells hindering their migration ability, arresting cell cycle through the modulation of retinoblastoma family proteins and specific cell cycle inhibitors, and ultimately inducing cancer cell death through apoptosis. The study, published in the Journal of Cellular Physiology, details findings by Daniela Barone and Letizia Cito, from the research group at the National Cancer Institute of Naples, Pascale Foundation, CROM, coordinated by Prof. Antonio Giordano, Director of the Sbarro Institute for Molecular Medicine, Temple University, Philadelphia Pa. “Our results prompt further assessment of the potential use of specific nutrients not only in the cancer prevention setting but also as a supportive strategy along with conventional therapies,” says Giordano. “Distinct species may exert different effects, in different stages of a certain neoplasm,” adds Barone. Gastric cancer is the fourth most common type of cancer worldwide and has been associated with genetic causes, Helicobacter pylori infection, and eating habits, such as consumption of smoked and salted food. Tomatoes are consumed worldwide and are a staple of the Mediterranean diet, which is popularly thought to lower cancer risk. Various tomato components have also been analyzed for their ability to counteract tumor growth in experimental systems, although few studies have analyzed the effects of tomatoes in their entirety. The study authors worked in collaboration with researchers from Barbara Nicolaus’ group and Rocco De Prisco at the National Research Council of Pozzuoli, Italy. “This work stems from the SHRO research program performed through a longstanding collaboration with the Department of Medicine, Surgery and Neuroscience, University of Siena, and the Pascale Institute, CROM of Mercogliano. On the wake of these results Dr Attilio Bianchi, General Director of the Pascale Institute and CROM, and I teamed up to renew the collaboration with SHRO implementing the nutrigenomics studies for the benefit of cancer patients,” concludes Giordano.
Portella L.,Instituto NAZIONALE PER LO STUDIO E LA CURA DEI TUMORI Fondazione Giovanni Pascale IRCCS ITALIA |
Vitale R.,CNR Institute of Biomolecular Chemistry |
De Luca S.,CNR Institute of Biostructure and Bioimaging |
D'Alterio C.,Instituto NAZIONALE PER LO STUDIO E LA CURA DEI TUMORI Fondazione Giovanni Pascale IRCCS ITALIA |
And 12 more authors.
PLoS ONE | Year: 2013
The CXCR4/CXCL12 axis plays a role in cancer metastases, stem cell mobilization and chemosensitization. Proof of concept for efficient CXCR4 inhibition has been demonstrated in stem cell mobilization prior to autologous transplantation in hematological malignancies. Nevertheless CXCR4 inhibitors suitable for prolonged use as required for anticancer therapy are not available. To develop new CXCR4 antagonists a rational, ligand-based approach was taken, distinct from the more commonly used development strategy. A three amino acid motif (Ar-Ar-X) in CXCL12, also found in the reverse orientation (X-Ar-Ar) in the vMIP-II inhibitory chemokine formed the core of nineteen cyclic peptides evaluated for inhibition of CXCR4-dependent migration, binding, P-ERK1/2-induction and calcium efflux. Peptides R, S and I were chosen for evaluation in in vivo models of lung metastases (B16-CXCR4 and KTM2 murine osteosarcoma cells) and growth of a renal cells xenograft. Peptides R, S, and T significantly reduced the association of the 12G5-CXCR4 antibody to the receptor and inhibited CXCL12-induced calcium efflux. The four peptides efficiently inhibited CXCL12-dependent migration at concentrations as low as 10 nM and delayed CXCL12-mediated wound healing in PES43 human melanoma cells. Intraperitoneal treatment with peptides R, I or S drastically reduced the number of B16-CXCR4-derived lung metastases in C57/BL mice. KTM2 osteosarcoma lung metastases were also reduced in Balb/C mice following CXCR4 inhibition. All three peptides significantly inhibited subcutaneous growth of SN12C-EGFP renal cancer cells. A novel class of CXCR4 inhibitory peptides was discovered. Three peptides, R, I and S inhibited lung metastases and primary tumor growth and will be evaluated as anticancer agents. © 2013 Portella et al.