title: Hierridin B Isolated from a Marine Cyanobacterium Alters VDAC1, Mitochondrial Activity, and Cell Cycle Genes on HT-29 Colon Adenocarcinoma Cells.
abstract: BACKGROUND
  Hierridin B was isolated from a marine cyanobacterium Cyanobium sp. strain and induced cytotoxicity selectively in HT-29 adenocarcinoma cells. The underlying molecular mechanism was not yet elucidated.
  
  
  METHODS
  HT-29 cells were exposed to the IC50 concentration of hierridin B (100.2 μM) for 48 h. Non-targeted proteomics was performed using 2D gel electrophoresis and MALDI-TOF/TOF mass spectrometry. The mRNA expression of apoptotic and cell cycle genes were analyzed by real-time PCR. Automated quantification of 160 cytoplasm and mitochondrial parameter was done by fluorescence microscopy using CellProfiler software.
  
  
  RESULTS
  Proteomics identified 21 significant different proteins, which belonged to protein folding/synthesis and cell structure amongst others. Increase of VDAC1 protein responsible for formation of mitochondrial channels was confirmed by mRNA expression. A 10-fold decrease of cytoskeleton proteins (STMN1, TBCA) provided a link to alterations of the cell cycle. CCNB1 and CCNE mRNA were decreased two-fold, and P21CIP increased 10-fold, indicative of cell cycle arrest. Morphological analysis of mitochondrial parameter confirmed a reduced mitochondrial activity.
  
  
  CONCLUSIONS
  Hierridin B is a potential anticancer compound that targets mitochondrial activity and function.
authors: Interdisciplinary Center of Marine and Environmental Research (CIIMAR/CIMAR), University of Porto, Rua dos Bragas 289, 4050-123 Porto, Portugal. freitas.srf.09@gmail.com.
authors: Sara
authors: S
authors: Freitas
authors: Interdisciplinary Center of Marine and Environmental Research (CIIMAR/CIMAR), University of Porto, Rua dos Bragas 289, 4050-123 Porto, Portugal. mrm@estsp.ipp.pt.|Health and Environmental Research Center (CISA), School of Apllied Health Sciences of Porto, Polytechnic Porto, Rua Valente Perfeito 322, 4400-330 Vila Nova de Gaia, Portugal. mrm@estsp.ipp.pt.|Department of Biology, Faculty of Sciences, University of Porto, Rua do Campo Alegre, Edifício FC4, 4169-007 Porto, Portugal. mrm@estsp.ipp.pt.|Institute for Molecular and Cell Biology (IBMC), University of Porto, Rua do Campo Alegre 823, 4150-180 Porto, Portugal. mrm@estsp.ipp.pt.
authors: Rosário
authors: R
authors: Martins
authors: Interdisciplinary Center of Marine and Environmental Research (CIIMAR/CIMAR), University of Porto, Rua dos Bragas 289, 4050-123 Porto, Portugal. costa.anamarg@gmail.com.
authors: Margarida
authors: M
authors: Costa
authors: Interdisciplinary Center of Marine and Environmental Research (CIIMAR/CIMAR), University of Porto, Rua dos Bragas 289, 4050-123 Porto, Portugal. pleao@ciimar.up.pt.
authors: Pedro N
authors: PN
authors: Leão
authors: Department of Medical Sciences, Institute of Biomedicine-iBiMED, University of Aveiro, 3810-193 Aveiro, Portugal. rvitorino@ua.pt.|Department of Physiology and Cardiothoracic Surgery, Faculty of Medicine, University of Porto, 4200-319 Porto, Portugal. rvitorino@ua.pt.
authors: Rui
authors: R
authors: Vitorino
authors: Interdisciplinary Center of Marine and Environmental Research (CIIMAR/CIMAR), University of Porto, Rua dos Bragas 289, 4050-123 Porto, Portugal. vmvascon@fc.up.pt.|Department of Biology, Faculty of Sciences, University of Porto, Rua do Campo Alegre, Edifício FC4, 4169-007 Porto, Portugal. vmvascon@fc.up.pt.
authors: Vitor
authors: V
authors: Vasconcelos
authors: Interdisciplinary Center of Marine and Environmental Research (CIIMAR/CIMAR), University of Porto, Rua dos Bragas 289, 4050-123 Porto, Portugal. rurbatzka@ciimar.up.pt.
authors: Ralph
authors: R
authors: Urbatzka
mesh_terms: D000840:Anisoles / Q000302:isolation & purification / Q000494:pharmacology*; D000964:Antimetabolites, Antineoplastic / Q000494:pharmacology*; D051017:Apoptosis Regulatory Proteins / Q000096:biosynthesis / Q000235:genetics; D000458:Cyanobacteria / Q000737:chemistry*; D003593:Cytoplasm / Q000187:drug effects / Q000378:metabolism; D018816:Genes, cdc / Q000187:drug effects*; D019073:HT29 Cells; D006801:Humans; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism*; D008958:Models, Molecular; D017510:Protein Folding / Q000187:drug effects; D040901:Proteomics; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D050995:Voltage-Dependent Anion Channel 1 / Q000187:drug effects*
chemical_list: D000840:Anisoles; D000964:Antimetabolites, Antineoplastic; D051017:Apoptosis Regulatory Proteins; D012333:RNA, Messenger; C494762:VDAC1 protein, human; C116944:hierridin B; D050995:Voltage-Dependent Anion Channel 1
keywords: anticancer drugs; bioactive compounds; cell cycle; colon cancer cells; high content analysis; marine cyanobacteria; mitochondria; natural products; proteomics; vdac1