Disulfiram Suppresses Invasive Ability of Osteosarcoma Cells Via the Inhibition of MMP-2 and MMP-9 Expression

Cho, Hyun-Ji; Lee, Tae-Sung; Park, Jae-Bok; Park, Kwan‐Kyu; Choe, Jung‐Yoon; Sin, Doo-Il; Park, Yoon-Yub; Moon, Yun-Seob; Lee, Kwang-Gill; Yeo, Joo‐Hong; Han, Sang‐Mi; Cho, Young-Su; Choi, Myeong-Rak; Park, Nam‐Gyu; Lee, Yun-Sik; Chang, Young‐Chae

doi:10.5483/bmbrep.2007.40.6.1069

Cited by 79 publications

(74 citation statements)

References 23 publications

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“…Human osteosarcoma cells produce high levels of matrix metalloproteinase (MMP)-2 and -9 (17,18), and HDAC inhibitors, including VPA have been shown to decrease the expression of MMP-2 and -9 in thyroid, gastric and lung cancer cells (19)(20)(21). Therefore, in this study, we investigated the effect of VPA on the mRNA expression of these MMPs in osteosarcoma cells and the roles of these MMPs in the cleavage of MICA and MICB on the cell surface.…”

Section: Introductionmentioning

confidence: 99%

Downregulation of matrix metalloproteinase-9 mRNA by valproic acid plays a role in inhibiting the shedding of MHC class I-related molecules A and B on the surface of human osteosarcoma cells

et al. 2012

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Abstract. Valproic acid, a histone deacetylase inhibitor, increases the expression of cell surface MHC class I-related chain molecules (MICs) A and B (MICA and B) in osteosarcoma cells and decreases their secretion of soluble MICA and MICB, which are produced by the proteolytic cleavage of cell surface MICs. Osteosarcoma cells have been reported to produce high levels of matrix metalloproteinase (MMP)-2 and -9. In this study, we investigated the involvement of MMP-2 and -9 in the inhibitory action of valproic acid (VPA) on the proteolytic cleavage of cell surface MICs using the U-2 OS and SaOS-2 osteosarcoma cell lines. VPA caused a marked decrease in the expression of MMP-9 mRNA in the U-2 OS and SaOS-2 cells and in the expression of MMP-2 mRNA in the U-2 OS cells, but only a slight decrease in the expression of MMP-2 mRNA in the SaOS-2 cells. The transfection of small interfering RNA (siRNA) for MMP-9 decreased the secretion of soluble MICA and MICB by both U-2 OS and SaOS-2 cells, but that of siRNA for MMP-2 did not. The present study therefore demonstrates that the downregulation of MMP-9 mRNA by VPA plays a role in the inhibitory action of VPA on the secretion of soluble MICA and MICB in osteosarcoma cells.

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Section: Introductionmentioning

confidence: 99%

Downregulation of matrix metalloproteinase-9 mRNA by valproic acid plays a role in inhibiting the shedding of MHC class I-related molecules A and B on the surface of human osteosarcoma cells

et al. 2012

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“…After 24 h, the cells on the apical side were wiped off with a Q-tip. Cells on the bottom of the filter were stained with hematoxylin (SigmaAldrich) and counted (three fields of each triplicate filter) with an inverted microscope (20).…”

Section: Matrigel Invasion Assaymentioning

confidence: 99%

Anti-invasive activity of histone deacetylase inhibitors via the induction of Egr-1 and the modulation of tight junction-related proteins in human hepatocarcinoma cells

Kim

Choi

Choi³

et al. 2009

BMB Reports

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“…Soluble MICA and B are produced by the proteolytic cleavage of cell-surface MICA and MICB by proteases, including matrix metalloproteinases (MMPs) (9,10), and human osteosarcomas have been reported to produce MMP-2 and -9 (33,34). Since it has been reported that HDAC inhibitors including VPA down-regulate the activity of MMPs in gastric, thyroid and lung cancer cells (36)(37)(38), the inhibitory effect of VPA on the production of soluble MICs may be ascribed to its inhibitory action on the activity of MMPs.…”

Section: Discussionmentioning

confidence: 99%

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

et al. 2012

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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 cellmediated 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 VPA with hydralazine further enhanced the effects. The present results suggest that combined administration of VPA and hydrazine is valuable for enhancing the therapeutic effects of immunotherapy for osteosarcomas.

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Disulfiram Suppresses Invasive Ability of Osteosarcoma Cells Via the Inhibition of MMP-2 and MMP-9 Expression

Cited by 79 publications

References 23 publications

Downregulation of matrix metalloproteinase-9 mRNA by valproic acid plays a role in inhibiting the shedding of MHC class I-related molecules A and B on the surface of human osteosarcoma cells

Downregulation of matrix metalloproteinase-9 mRNA by valproic acid plays a role in inhibiting the shedding of MHC class I-related molecules A and B on the surface of human osteosarcoma cells

Anti-invasive activity of histone deacetylase inhibitors via the induction of Egr-1 and the modulation of tight junction-related proteins in human hepatocarcinoma cells

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

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