title: NF-κB mediates the antiproliferative and proapoptotic effects of bergamot juice in HepG2 cells.
abstract: OBJECTIVE
  Among cancers, hepatocellular carcinoma is one of the commonest worldwide, and its incidence is increasing around the world. A lot of evidence underlines that natural substances usually consumed in the diet can have an important role in the prevention of cancer. In this study we investigated the molecular mechanisms underlying the antiproliferative activity of Citrus bergamia (bergamot) juice (BJ) in human hepatocellular carcinoma HepG2 cells.
  
  
  METHODS
  HepG2 cells were exposed to BJ and then cell proliferation, cell cycle progression, apoptosis and NF-κB nuclear translocation were evaluated.
  
  
  RESULTS
  Here we present results demonstrating that BJ reduced the growth rate of human hepatocellular carcinoma HepG2 cells in a time- and concentration-dependent manner, by a mechanism involving the activation of apoptotic machinery via both intrinsic and extrinsic pathways. Moreover, BJ increased expression of P53 and P21 proteins that may be responsible for the HepG2 cell cycle arrest in G2 phase. In addition, BJ reduced NF-κB nuclear translocation.
  
  
  CONCLUSIONS
  Our data demonstrate the ability of BJ in reducing the growth of HepG2 cells, revealing its mechanism of action and suggesting a promising role as anticancer drugs.
authors.affiliation: Department of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, Messina, Italy.
authors.forename: Nadia
authors.initials: N
authors.lastname: Ferlazzo
authors.affiliation: Department of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, Messina, Italy.
authors.forename: Santa
authors.initials: S
authors.lastname: Cirmi
authors.affiliation: Department of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, Messina, Italy.
authors.forename: Marina
authors.initials: M
authors.lastname: Russo
authors.affiliation: Department of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, Messina, Italy.
authors.forename: Elena
authors.initials: E
authors.lastname: Trapasso
authors.affiliation: Department of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, Messina, Italy.
authors.forename: Maria Rita
authors.initials: MR
authors.lastname: Ursino
authors.affiliation: Department of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, Messina, Italy.
authors.forename: Giovanni Enrico
authors.initials: GE
authors.lastname: Lombardo
authors.affiliation: Department of Clinical and Experimental Medicine, University of Messina, Messina, Italy; Institute of Applied Sciences and Intelligent Systems, ISASI CNR, Messina, Italy.
authors.forename: Sebastiano
authors.initials: S
authors.lastname: Gangemi
authors.affiliation: Department of Biomedical and Dental Sciences and Morphofunctional imaging, University of Messina, Messina, Italy.
authors.forename: Gioacchino
authors.initials: G
authors.lastname: Calapai
authors.affiliation: Department of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, Messina, Italy. Electronic address: mnavarra@unime.it.
authors.forename: Michele
authors.initials: M
authors.lastname: Navarra
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D002453:Cell Cycle / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects*; D020552:Comet Assay; D004249:DNA Damage; D018076:DNA, Complementary / Q000096:biosynthesis / Q000235:genetics; D016195:G2 Phase / Q000187:drug effects; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects / Q000235:genetics; D016158:Genes, p53 / Q000187:drug effects; D056945:Hep G2 Cells; D006571:Heterocyclic Compounds / Q000737:chemistry; D006801:Humans; D016328:NF-kappa B / Q000378:metabolism*; D015689:Oncogene Protein p21(ras) / Q000187:drug effects / Q000235:genetics; D010936:Plant Extracts / Q000494:pharmacology*; D012334:RNA, Neoplasm / Q000096:biosynthesis; D014178:Translocation, Genetic
chemical_list: D018076:DNA, Complementary; D006571:Heterocyclic Compounds; D016328:NF-kappa B; D010936:Plant Extracts; D012334:RNA, Neoplasm; D015689:Oncogene Protein p21(ras)
keywords: Antiproliferative activity; Apoptosis; Citrus bergamia; Complementary medicine; Flavonoids; HepG2 cells; Natural products