1. Academic Validation
  2. Antiproliferative and Antiangiogenic Effects of Punica granatum Juice (PGJ) in Multiple Myeloma (MM)

Antiproliferative and Antiangiogenic Effects of Punica granatum Juice (PGJ) in Multiple Myeloma (MM)

  • Nutrients. 2016 Oct 1;8(10):611. doi: 10.3390/nu8100611.
Daniele Tibullo 1 2 Nunzia Caporarello 3 Cesarina Giallongo 4 5 Carmelina Daniela Anfuso 6 Claudia Genovese 7 8 Carmen Arlotta 9 10 Fabrizio Puglisi 11 Nunziatina L Parrinello 12 Vincenzo Bramanti 13 Alessandra Romano 14 Gabriella Lupo 15 Valeria Toscano 16 Roberto Avola 17 Maria Violetta Brundo 18 Francesco Di Raimondo 19 Salvatore Antonio Raccuia 20 21
Affiliations

Affiliations

  • 1 Section of Hematology, Department of Surgery and Medical Specialties, University of Catania, Catania 95125, Italy. [email protected].
  • 2 Department of Biological, Geological and Environmental Sciences, University of Catania, Catania 95125, Italy. [email protected].
  • 3 Department of Biomedical and Biotechnological Sciences, University of Catania, Catania 95125, Italy. [email protected].
  • 4 Section of Hematology, Department of Surgery and Medical Specialties, University of Catania, Catania 95125, Italy. [email protected].
  • 5 Department of Biomedical and Biotechnological Sciences, University of Catania, Catania 95125, Italy. [email protected].
  • 6 Department of Biomedical and Biotechnological Sciences, University of Catania, Catania 95125, Italy. [email protected].
  • 7 Department of Biological, Geological and Environmental Sciences, University of Catania, Catania 95125, Italy. [email protected].
  • 8 Institute for Agricultural and Forest Systems in the Mediterranean, National Research Council, Catania 95125, Italy. [email protected].
  • 9 Department of Biological, Geological and Environmental Sciences, University of Catania, Catania 95125, Italy. [email protected].
  • 10 Institute for Agricultural and Forest Systems in the Mediterranean, National Research Council, Catania 95125, Italy. [email protected].
  • 11 Section of Hematology, Department of Surgery and Medical Specialties, University of Catania, Catania 95125, Italy. [email protected].
  • 12 Section of Hematology, Department of Surgery and Medical Specialties, University of Catania, Catania 95125, Italy. [email protected].
  • 13 Department of Biomedical and Biotechnological Sciences, University of Catania, Catania 95125, Italy. [email protected].
  • 14 Section of Hematology, Department of Surgery and Medical Specialties, University of Catania, Catania 95125, Italy. [email protected].
  • 15 Department of Biomedical and Biotechnological Sciences, University of Catania, Catania 95125, Italy. [email protected].
  • 16 Institute for Agricultural and Forest Systems in the Mediterranean, National Research Council, Catania 95125, Italy. [email protected].
  • 17 Department of Biomedical and Biotechnological Sciences, University of Catania, Catania 95125, Italy. [email protected].
  • 18 Department of Biological, Geological and Environmental Sciences, University of Catania, Catania 95125, Italy. [email protected].
  • 19 Section of Hematology, Department of Surgery and Medical Specialties, University of Catania, Catania 95125, Italy. [email protected].
  • 20 Department of Biological, Geological and Environmental Sciences, University of Catania, Catania 95125, Italy. [email protected].
  • 21 Institute for Agricultural and Forest Systems in the Mediterranean, National Research Council, Catania 95125, Italy. [email protected].
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.

Keywords

Punica granatum juice; angiogenesis; multiple myeloma; proliferation.

Figures