Sulforaphane induces ROS mediated induction of NKG2D ligands in human cancer cell lines and enhances susceptibility to NK cell mediated lysis

Life Sci. 2015 Apr 1;126:19-27. doi: 10.1016/j.lfs.2015.01.026. Epub 2015 Feb 24.

Abstract

Aims: 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.

Main 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.

Key findings: 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.

Significance: Our results indicate that SFN has an immunotherapeutic potential to be used in cancer therapy.

Keywords: Ionizing radiation; MICA/MICB; NK cells; ROS; Sulforaphane.

Publication types

  • Clinical Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anticarcinogenic Agents / pharmacology*
  • Female
  • Gene Expression Regulation, Neoplastic / drug effects
  • Gene Expression Regulation, Neoplastic / physiology
  • Histocompatibility Antigens Class I / immunology
  • Humans
  • Immunity, Cellular / drug effects
  • Isothiocyanates / pharmacology*
  • Killer Cells, Natural / immunology*
  • Killer Cells, Natural / pathology
  • Male
  • NK Cell Lectin-Like Receptor Subfamily K / immunology*
  • Neoplasms / drug therapy
  • Neoplasms / immunology*
  • Neoplasms / pathology
  • Reactive Oxygen Species / immunology*
  • U937 Cells

Substances

  • Anticarcinogenic Agents
  • Histocompatibility Antigens Class I
  • Isothiocyanates
  • KLRK1 protein, human
  • MHC class I-related chain A
  • MICB antigen
  • NK Cell Lectin-Like Receptor Subfamily K
  • Reactive Oxygen Species
  • sulforaphane