title: The Urtica dioica extract enhances sensitivity of paclitaxel drug to MDA-MB-468 breast cancer cells.
abstract: BACKGROUND
  Due to the chemo resistant nature of cancer cells and adverse effects of current therapies, researchers are looking for the most efficient therapeutic approach which has the lowest side effects and the highest toxicity on cancer cells. The aim of the present study was to investigate the synergic effect of Urtica dioica extract in combination with paclitaxel on cell death and invasion of human breast cancer MDA-MB-468 cell line.
  
  
  METHODS
  To determine the cytotoxic effects of Urtica dioica extract with paclitaxel, MTT assay was performed. The scratch test was exploited to assess the effects of Urtica dioica, Paclitaxel alone and combination on migration of cancer cells. The expression levels of snail-1, ZEB1, ZEB2, twist, Cdc2, cyclin B1 and Wee1 genes were quantified using qRT-PCR and western blot performed for snail-1expression. The effects of plant extract, Paclitaxel alone and combination on different phases of cell cycle was analyzed using flow cytometry.
  
  
  RESULTS
  Results of MTT assay showed that Urtica dioica significantly destroyed cancer cells. Interestingly, Concurrent use of Urtica dioica extract with paclitaxel resulted in decreased IC50 dose of paclitaxel. Moreover, findings of scratch assay exhibited the inhibitory effects of Urtica dioica, Paclitaxel alone and combination on migration of MDA-MB-468 cell line. Our findings also demonstrated that the extract substantially decreased the Snail-1 and related gene expression. Ultimately, Cell cycle arrest occurred at G2/M phase post-treatment by deregulating Cdc2 and wee1.
  
  
  CONCLUSIONS
  Our results demonstrated that the dichloromethane extract of Urtica dioica inhibit cell growth and migration. Also, Urtica dioica extract substantially increased sensitivity of breast cancer cells to paclitaxel. Therefore, it can be used as a potential candidate for treatment of breast cancer with paclitaxel.
authors: Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran; Student Research Committee, Tabriz University of Medical Sciences, Tabriz, Iran.
authors: Ali
authors: A
authors: Mohammadi
authors: Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran; Student Research Committee, Tabriz University of Medical Sciences, Tabriz, Iran.
authors: Behzad
authors: B
authors: Mansoori
authors: Department of Pathobiology, Faculty of Veterinary Medicine, University of Tabriz, Tabriz, Iran.
authors: Mahyar
authors: M
authors: Aghapour
authors: Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.
authors: Solmaz
authors: S
authors: Shirjang
authors: Department of mycology, Health school, Tehran University of Medical Sciences, Tehran, Iran.
authors: Sanam
authors: S
authors: Nami
authors: Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran. Electronic address: behzad_im@yahoo.com.
authors: Behzad
authors: B
authors: Baradaran
mesh_terms: D001943:Breast Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D016203:CDC2 Protein Kinase; D059447:Cell Cycle Checkpoints / Q000187:drug effects; D018797:Cell Cycle Proteins / Q000378:metabolism; D016923:Cell Death / Q000187:drug effects; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D018844:Cyclin-Dependent Kinases / Q000378:metabolism; D004357:Drug Synergism; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D020128:Inhibitory Concentration 50; D009687:Nuclear Proteins / Q000378:metabolism; D017239:Paclitaxel / Q000494:pharmacology / Q000627:therapeutic use*; D010936:Plant Extracts / Q000494:pharmacology / Q000627:therapeutic use*; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D000071250:Snail Family Transcription Factors / Q000235:genetics / Q000378:metabolism; D026982:Urtica dioica / Q000737:chemistry*; D014945:Wound Healing / Q000187:drug effects
chemical_list: D018797:Cell Cycle Proteins; D009687:Nuclear Proteins; D010936:Plant Extracts; D012333:RNA, Messenger; D000071250:Snail Family Transcription Factors; D011505:Protein-Tyrosine Kinases; C499349:WEE1 protein, human; D016203:CDC2 Protein Kinase; C528899:CDK1 protein, human; D018844:Cyclin-Dependent Kinases; D017239:Paclitaxel
keywords: Apoptosis; Cytotoxicity; MDA-MB-468; Paclitaxel; Urtica dioica extract