The anti-cancer compound Nordy inhibits CXCR4-mediated production of IL-8 and VEGF by malignant human glioma cells

Abstract

The chemokine receptor CXCR4 plays an important role in tumor growth, angiogenesis and metastasis. Our previous studies showed that Nordy, a synthetic chiral compound of nordihydroguaiaretic acid, inhibited the growth and angiogenesis of various malignant tumors. In this study we examined the capacity of Nordy to regulate CXCR4-mediated production of angiogenic factors by human glioblastoma cells. We found that Nordy potently inhibited CXCR4 ligand SDF-1-induced production of IL-8 and vascular endothelial cell growth factor, two important angiogenic factors implicated in the progression of malignant tumors. Further study revealed that the effect of Nordy was attributable to its down-regulation of the expression of functional CXCR4 in glioblastoma cells. These results suggest that the anti-cancer activity of Nordy is due, at least in part, to its suppression of the chemokine receptor CXCR4 thus reducing the production of angiogenic factors by tumor cells.

Umbilical Cord Blood-Derived Mesenchymal Stem Cells Inhibit, But Adipose Tissue-Derived Mesenchymal Stem Cells Promote, Glioblastoma Multiforme Proliferation

“…In addition, the inhibition of the CXCL12/CXCR4 axis generates impairment of tumor-producing angiogenic factors, such as interleukin-8 and VEGF, resulting in the failure of tumor angiogenesis [58,59]. CXCL12 expression is crucial for tumor development associated with the tumor cell survival and tumor angiogenesis.…”

Chemokines and Chemokine Receptors Expression in the Adipose Derived Stem Cells (ASCs), Breast Tissues and in Peripheral Blood of Patients with Breast Cancer

“…Brand and colleagues have demonstrated that ASC-derived SDF-1 stimulation induces a significant increase in proangiogenic factors such as VEGF protein levels [32]. Furthermore, it has been reported that SDF-1 may contribute to the production of other angiogenic factors such as IL-8 and MMP-3 by tumor cells through both receptors, CXCR4 and CXCR7 [4,8].…”

“…They succeeded to inhibit the breast cancer metastasis using a CXCR4 neutralizing antibody [7]. Moreover, CXCR4 may contribute to the production of angiogenic factors such as interleukin-8 (IL-8) and vascular endothelial growth factor (VEGF) by tumor cells [8]. Through angiogenesis, regulated upon activation, normal T cell expressed and secreted (RANTES) and monocyte chemotactic protein (MCP)-1 has also been reported to have tumor promoting effects [9].…”

Synthetic Polypeptide Derived from Viral Macrophage Inflammatory Protein II Inhibit VEGF Production of Human Glioma U87 Cells through SDF-1α/CXCR4-Mediated AKT Signaling Pathway

“…For RT-PCR to detect SDF-1, VEGF and CXCR4 mRNA expression, 1 μg of total RNA from U87 cells treated with different factors was subjected to RT-PCR using two-step RT-PCR kit according to the protocol described by the supplier. Each PCR reaction and the PCR products analyses were performed as described in [14]. The primer pairs were as follows: β-actin …”