title: Antiproliferative and Antiangiogenic Effects of Punica granatum Juice (PGJ) in Multiple Myeloma (MM).
abstract: Multiple myeloma (MM) is a clonal B-cell malignancy characterized by an accumulation of clonal plasma cells (PC) in the bone marrow (BM) leading to bone destruction and BM failure. Despite recent advances in pharmacological therapy, MM remains a largely incurable pathology. Therefore, novel effective and less toxic agents are urgently necessary. In the last few years, pomegranate has been studied for its potential therapeutic properties including treatment and prevention of cancer. Pomegranate juice (PGJ) contains a number of potential active compounds including organic acids, vitamins, sugars, and phenolic components that are all responsible of the pro-apoptotic effects observed in tumor cell line. The aim of present investigation is to assess the antiproliferative and antiangiogenic potential of the PGJ in human multiple myeloma cell lines. Our data demonstrate the anti-proliferative potential of PGJ in MM cells; its ability to induce G0/G1 cell cycle block and its anti-angiogenic effects. Interestingly, sequential combination of bortezomib/PGJ improved the cytotoxic effect of the proteosome inhibitor. We investigated the effect of PGJ on angiogenesis and cell migration/invasion. Interestingly, we observed an inhibitory effect on the tube formation, microvessel outgrowth aorting ring and decreased cell migration and invasion as showed by wound-healing and transwell assays, respectively. Analysis of angiogenic genes expression in endothelial cells confirmed the anti-angiogenic properties of pomegranate. Therefore, PGJ administration could represent a good tool in order to identify novel therapeutic strategies for MM treatment, exploiting its anti-proliferative and anti-angiogenic effects. Finally, the present research supports the evidence that PGJ could play a key role of a future therapeutic approach for treatment of MM in order to optimize the pharmacological effect of bortezomib, especially as adjuvant after treatment.
authors.affiliation: Section of Hematology, Department of Surgery and Medical Specialties, University of Catania, Catania 95125, Italy. d.tibullo@unict.it.|Department of Biological, Geological and Environmental Sciences, University of Catania, Catania 95125, Italy. d.tibullo@unict.it.
authors.forename: Daniele
authors.initials: D
authors.lastname: Tibullo
authors.affiliation: Department of Biomedical and Biotechnological Sciences, University of Catania, Catania 95125, Italy. nunzia.caporarello@gmail.com.
authors.forename: Nunzia
authors.initials: N
authors.lastname: Caporarello
authors.affiliation: Section of Hematology, Department of Surgery and Medical Specialties, University of Catania, Catania 95125, Italy. cesarinagiallongo@yahoo.it.|Department of Biomedical and Biotechnological Sciences, University of Catania, Catania 95125, Italy. cesarinagiallongo@yahoo.it.
authors.forename: Cesarina
authors.initials: C
authors.lastname: Giallongo
authors.affiliation: Department of Biomedical and Biotechnological Sciences, University of Catania, Catania 95125, Italy. anfudan@unict.it.
authors.forename: Carmelina Daniela
authors.initials: CD
authors.lastname: Anfuso
authors.affiliation: Department of Biological, Geological and Environmental Sciences, University of Catania, Catania 95125, Italy. claudia.genovese@cnr.it.|Institute for Agricultural and Forest Systems in the Mediterranean, National Research Council, Catania 95125, Italy. claudia.genovese@cnr.it.
authors.forename: Claudia
authors.initials: C
authors.lastname: Genovese
authors.affiliation: Department of Biological, Geological and Environmental Sciences, University of Catania, Catania 95125, Italy. carmen.arlotta@isafom.cnr.it.|Institute for Agricultural and Forest Systems in the Mediterranean, National Research Council, Catania 95125, Italy. carmen.arlotta@isafom.cnr.it.
authors.forename: Carmen
authors.initials: C
authors.lastname: Arlotta
authors.affiliation: Section of Hematology, Department of Surgery and Medical Specialties, University of Catania, Catania 95125, Italy. puglisi.fabri@gmail.com.
authors.forename: Fabrizio
authors.initials: F
authors.lastname: Puglisi
authors.affiliation: Section of Hematology, Department of Surgery and Medical Specialties, University of Catania, Catania 95125, Italy. lauraparrinello@tiscali.it.
authors.forename: Nunziatina L
authors.initials: NL
authors.lastname: Parrinello
authors.affiliation: Department of Biomedical and Biotechnological Sciences, University of Catania, Catania 95125, Italy. V.bramanti@unict.it.
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Bramanti
authors.affiliation: Section of Hematology, Department of Surgery and Medical Specialties, University of Catania, Catania 95125, Italy. alessandraromano@google.it.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Romano
authors.affiliation: Department of Biomedical and Biotechnological Sciences, University of Catania, Catania 95125, Italy. lupogab@unict.it.
authors.forename: Gabriella
authors.initials: G
authors.lastname: Lupo
authors.affiliation: Institute for Agricultural and Forest Systems in the Mediterranean, National Research Council, Catania 95125, Italy. valeria.toscano@cnr.it.
authors.forename: Valeria
authors.initials: V
authors.lastname: Toscano
authors.affiliation: Department of Biomedical and Biotechnological Sciences, University of Catania, Catania 95125, Italy. alessandraromano@google.it.
authors.forename: Roberto
authors.initials: R
authors.lastname: Avola
authors.affiliation: Department of Biological, Geological and Environmental Sciences, University of Catania, Catania 95125, Italy. mvbrundo@unict.it.
authors.forename: Maria Violetta
authors.initials: MV
authors.lastname: Brundo
authors.affiliation: Section of Hematology, Department of Surgery and Medical Specialties, University of Catania, Catania 95125, Italy. diraimon@unict.it.
authors.forename: Francesco
authors.initials: F
authors.lastname: Di Raimondo
authors.affiliation: Department of Biological, Geological and Environmental Sciences, University of Catania, Catania 95125, Italy. salvatore.raccuia@cnr.it.|Institute for Agricultural and Forest Systems in the Mediterranean, National Research Council, Catania 95125, Italy. salvatore.raccuia@cnr.it.
authors.forename: Salvatore Antonio
authors.initials: SA
authors.lastname: Raccuia
mesh_terms: D020533:Angiogenesis Inhibitors / Q000494:pharmacology*; D000972:Antineoplastic Agents, Phytogenic; D000975:Antioxidants / Q000494:pharmacology; D001628:Beverages; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D005419:Flavonoids; D005638:Fruit / Q000737:chemistry*; D006801:Humans; D029561:Lythraceae; D009101:Multiple Myeloma / Q000098:blood supply / Q000188:drug therapy* / Q000473:pathology; D009361:Neoplasm Invasiveness / Q000517:prevention & control; D008517:Phytotherapy; D013634:Tannins; D042461:Vascular Endothelial Growth Factor A / Q000494:pharmacology
chemical_list: D020533:Angiogenesis Inhibitors; D000972:Antineoplastic Agents, Phytogenic; D000975:Antioxidants; D005419:Flavonoids; D013634:Tannins; D042461:Vascular Endothelial Growth Factor A
keywords: Punica granatum juice; angiogenesis; multiple myeloma; proliferation