Valproic acid cooperates with hydralazine to augment the susceptibility of human osteosarcoma cells to Fas- and NK cell-mediated cell death

International Journal of Oncology
Koji YamanegiNobuyuki Terada

Abstract

We investigated the effects of valproic acid (VPA), a histone deacetylase inhibitor, in combination with hydralazine, a DNA methylation inhibitor, on the expression of cell-surface Fas and MHC-class I-related chain molecules A and B (MICA and B), the ligands of NKG2D which is an activating receptor of NK cells, and on production of their soluble forms in HOS, U-2 OS and SaOS-2 human osteosarcoma cell lines. We also examined the susceptibility of these cells to Fas- and NK cell-mediated cell death. VPA did not increase the expression of Fas on the surface of osteosarcoma cells, while hydralazine did, and the combination of VPA with hydralazine increased the expression of cell-surface Fas. In contrast, the combination of VPA with hydralazine did not increase the production of soluble Fas by osteosarcoma cells. Both VPA and hydralazine increased the expression of cell-surface MICA and B in osteosarcoma cells, and their combination induced a greater increase in their expression. VPA inhibited the production of both soluble MICA and MICB by osteosarcoma cells while hydralazine produced no effect. Both VPA and hydralazine enhanced the susceptibility of osteosarcoma cells to Fas- and NK cell-mediated cell death and the combination of ...Continue Reading

Citations

Jan 5, 2014·Pharmacology & Therapeutics·Luca SigalottiMichele Maio
Aug 19, 2015·Frontiers in Oncology·Malgorzata WachowskaJakub Golab
Jul 23, 2014·Oncoimmunology·Aroa Baragaño RanerosCarlos López-Larrea
Feb 24, 2015·Frontiers in Immunology·Erika HéningerJoshua M Lang
Dec 7, 2019·Cancers·Lucillia BezuOliver Kepp
Jun 4, 2019·Frontiers in Immunology·Zenan WangZhaoming Ye
Dec 17, 2020·Cancers·Mieszko LachotaKarl-Johan Malmberg

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