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.