title: Sulforaphane induces ROS mediated induction of NKG2D ligands in human cancer cell lines and enhances susceptibility to NK cell mediated lysis.
abstract: OBJECTIVE
  The goal of this study is to investigate the tumor cytotoxic effects of sulforaphane (SFN) and ionizing radiation (IR) as well as their ability to up-regulate natural killer group 2, member D (NKG2D) ligands and modulate the susceptibility of tumor cells to natural killer (NK) cell-mediated killing.
  
  
  METHODS
  Expression of MHC class I-related chain molecules A and B (MICA/MICB) and total reactive oxygen species (ROS) were assessed by flow cytometry following labeling with appropriate dyes or antibodies. NK cell cytotoxicity was determined by calcein release of target cells.
  
  
  RESULTS
  The expression of NKG2D ligands MICA/MICB was found to vary in all the four tumor cell lines tested (MCF7 < A549 < MDA-MB-231 < U937). Exposure of these cells to IR and SFN resulted in a differential induction of these ligands. IR induced an increase in expression of MICA/MICB in MCF7 cells and SFN induced MICA/MICB expression in A549 and MDA-MB-231 cells. This SFN induced increase in receptor expression resulted in increased susceptibility to NK cell mediated killing of tumor cells which was abrogated by blocking with anti-MICA/MICB antibody. SFN induced increase in MICA/MICB expression as well as increased susceptibility to NK cell mediated killing was abrogated by N-acetyl cysteine in A549 and MDA-MB-231 cells suggesting a ROS mediated mechanism.
  
  
  CONCLUSIONS
  Our results indicate that SFN has an immunotherapeutic potential to be used in cancer therapy.
authors.affiliation: Immunology Section, Radiation Biology & Health Sciences Division, Bio-Science Group, Bhabha Atomic Research Centre, Mumbai 400 085, India.
authors.forename: Prayag J
authors.initials: PJ
authors.lastname: Amin
authors.affiliation: Immunology Section, Radiation Biology & Health Sciences Division, Bio-Science Group, Bhabha Atomic Research Centre, Mumbai 400 085, India. Electronic address: bshankar@barc.gov.in.
authors.forename: Bhavani S
authors.initials: BS
authors.lastname: Shankar
mesh_terms: D016588:Anticarcinogenic Agents / Q000494:pharmacology*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects / Q000502:physiology; D015395:Histocompatibility Antigens Class I / Q000276:immunology; D006801:Humans; D007111:Immunity, Cellular / Q000187:drug effects; D017879:Isothiocyanates / Q000494:pharmacology*; D007694:Killer Cells, Natural / Q000276:immunology* / Q000473:pathology; D008297:Male; D055655:NK Cell Lectin-Like Receptor Subfamily K / Q000276:immunology*; D009369:Neoplasms / Q000188:drug therapy / Q000276:immunology* / Q000473:pathology; D017382:Reactive Oxygen Species / Q000276:immunology*; D013454:Sulfoxides; D020298:U937 Cells
chemical_list: D016588:Anticarcinogenic Agents; D015395:Histocompatibility Antigens Class I; D017879:Isothiocyanates; C527085:KLRK1 protein, human; C099187:MHC class I-related chain A; C098080:MICB antigen; D055655:NK Cell Lectin-Like Receptor Subfamily K; D017382:Reactive Oxygen Species; D013454:Sulfoxides; C016766:sulforaphane
keywords: Ionizing radiation; MICA/MICB; NK cells; ROS; Sulforaphane