Heme oxygenase-1 inhibits breast cancer invasion via suppressing the expression of matrix metalloproteinase-9

Abstract

In the present study, we investigated the antitumor effects of the invasiveness and migration of heme oxygenase 1 (HO-1) in human breast carcinoma cells. 12-O-tetradecanoylphorbol-13-acetate (TPA) -induced matrix metalloproteinase-9 (MMP-9) enzyme activity and gene expression at both protein and mRNA levels were examined in human breast carcinoma cells (MCF-7 and MDA-MB-231), and the addition of the MMP-9 inhibitor, SB3CT, significantly suppressed TPA-induced invasion and migration according to the in vitro Transwell assay. Elevation of HO-1 gene expression by ferric protoporphyrin IX inhibited TPA-induced invasion of MCF-7 cells, which was blocked by adding the heme oxygenase inhibitor, tin protoporphyrin IX, or transfection of cells with HO-1 short hairpin RNA. MCF-7 cells overexpressing HO-1 (MCF-7/HO-1) were established in the present study, and TPA-induced MMP-9 gene expression, tumor invasion, and colony formation were significantly reduced in MCF-7/HO-1 cells, compared with those in Neo-transfected cells. Activation of protein kinase CA/extracellular signalregulated kinases/AP-1 with stimulation of reactive oxygen species production was involved in TPA-induced invasion of MCF-7 cells, which was attenuated by HO-1 protein induced by ferric protoporphyrin IX or transfection of HO-1 expression vectors. Additionally, the addition of carbon monoxide, but not ferric ions, biliverdin, or bilirubin, inhibited TPA-induced invasion through suppressing MMP-9, extracellular signal-regulated kinases, and AP-1 activation stimulated by TPA. The beneficial role of HO-1 in blocking tumor invasion was first identified in this study.

Celastrol Inhibits Breast Cancer Cell Invasion via Suppression of NF-ĸB-mediated Matrix Metalloproteinase-9 Expression

“…PMA has been used as a tumor promoter in chemical-induced carcinogenesis in vitro and in vivo. Previous studies showed that PMA is able to promote tumor migration and invasion by stimulating MMP-2 or MMP-9 expression in glioma, colon, hepatoma, and breast cancer cells [28,29]. However, the mechanism by which PMA induces breast cancer cell invasion has not been known.…”

Transcriptome Analysis of Piperlongumine-Treated Human Pancreatic Cancer Cells Reveals Involvement of Oxidative Stress and Endoplasmic Reticulum Stress Pathways

“…However, HMOX-1 can induce cancer cell apoptosis and inhibit tumor cell motility. 30,31 Recently, HMOX-1 expression was shown to be elevated by PL in breast cancer cells and a determining factor in the differential response of normal breast cells to PL. 32 Interestingly, PL silenced ATP-binding cassette subfamily B, member 10 (ABCB10) expression.…”

BMP-6 inhibits MMP-9 expression by regulating heme oxygenase-1 in MCF-7 breast cancer cells

“…Given that HO-1 represses MMP-9 activation during the inhibition of breast cancer progression (Lin et al 2008), it is opening the possibility that BMP-6 induction is, at least partially, responsible for the down-regulation of MMP-9 expression. Therefore, we detected BMP-6-regulated expression of MMP-9 in MCF-7 cells.…”