Suradista NSC 651016 inhibits the angiogenic activity of CXCL12-stromal cell-derived factor 1alpha.

CXCL12 (stromal cell-derived factor 1alpha), a ligand for CXCR4, has been shown to induce endothelial cell chemotaxis and to stimulate angiogenesis, suggesting that it may be a significant target for antiangiogenic therapy. Here we have tested suradista NSC 651016, a compound known to inhibit CXCL12-induced monocyte chemotaxis, for its ability to inhibit CXCL12-induced angiogenic activity. NSC 651016 inhibited CXCL12-mediated endothelial cell chemotaxis in a dose-dependent manner. In addition, new vessel sprouting, by both rat and chick aorta in an angiogenesis model, was inhibited. Additionally, in vitro capillary-like structure formation induced by CXCL12 was inhibited by NSC 651016. Furthermore, NSC 651016 inhibited CXCL12-mediated angiogenesis in an in vivo s.c. assay. These data indicate that suradista NSC 651016 possesses in vitro and in vivo antiangiogenic activity and has the potential to interfere with neovacularization of tumors and their metastases.

[1]  P. Piccioli,et al.  Stromal cell‐derived factor‐1α induces astrocyte proliferation through the activation of extracellular signal‐regulated kinases 1/2 pathway , 2001, Journal of neurochemistry.

[2]  T. Mcclanahan,et al.  Involvement of chemokine receptors in breast cancer metastasis , 2001, Nature.

[3]  Chulhee Choi,et al.  CXC Chemokine Receptor 4 Expression and Function in Human Astroglioma Cells1 , 2001, The Journal of Immunology.

[4]  M. Imamura,et al.  Expression of stromal cell-derived factor 1 and CXCR4 ligand receptor system in pancreatic cancer: a possible role for tumor progression. , 2000, Clinical cancer research : an official journal of the American Association for Cancer Research.

[5]  Fabrizio Manetti,et al.  Research on anti-HIV-1 agents. Investigation on the CD4-Suradista binding mode through docking experiments , 2000, J. Comput. Aided Mol. Des..

[6]  N. Tarasova,et al.  Small molecule inhibitor of HIV‐1 cell fusion blocks chemokine receptor‐mediated function , 1998, Journal of leukocyte biology.

[7]  Masahiko Kuroda,et al.  Function of the chemokine receptor CXCR4 in haematopoiesis and in cerebellar development , 1998, Nature.

[8]  Kouji Matsushima,et al.  The chemokine receptor CXCR4 is essential for vascularization of the gastrointestinal tract , 1998, Nature.

[9]  M. Hollingshead,et al.  Inhibition of in vitro and in vivo HIV replication by a distamycin analogue that interferes with chemokine receptor function: a candidate for chemotherapeutic and microbicidal application. , 1998, Journal of medicinal chemistry.

[10]  E. Ohlstein,et al.  Chemokine Receptors in Human Endothelial Cells , 1998, The Journal of Biological Chemistry.

[11]  M. Baggiolini,et al.  Two murine homologues of the human chemokine receptor CXCR4 mediating stromal cell‐derived factor 1α activation of Gi2 are differentially expressed in vivo , 1997, European journal of immunology.

[12]  M. Epstein,et al.  Inhibition of growth factor mitogenicity and growth of tumor cell xenografts by a sulfonated distamycin A derivative. , 1997, Pharmacology.

[13]  Bernhard Moser,et al.  The CXC chemokine SDF-1 is the ligand for LESTR/fusin and prevents infection by T-cell-line-adapted HIV-1 , 1996, Nature.

[14]  J. Sodroski,et al.  The lymphocyte chemoattractant SDF-1 is a ligand for LESTR/fusin and blocks HIV-1 entry , 1996, Nature.

[15]  S. Nishikawa,et al.  Defects of B-cell lymphopoiesis and bone-marrow myelopoiesis in mice lacking the CXC chemokine PBSF/SDF-1 , 1996, Nature.

[16]  R. Kiser,et al.  Novel sulfonated and phosphonated analogs of distamycin which inhibit the replication of HIV. , 1995, Antiviral research.

[17]  H. Kikutani,et al.  Molecular cloning and structure of a pre-B-cell growth-stimulating factor. , 1994, Proceedings of the National Academy of Sciences of the United States of America.

[18]  M. Ciomei,et al.  New sulfonated distamycin A derivatives with bFGF complexing activity. , 1994, Biochemical pharmacology.

[19]  Allen D. Delaney,et al.  Molecular cloning of the cDNA and chromosomal localization of the gene for a putative seven-transmembrane segment (7-TMS) receptor isolated from human spleen. , 1993, Genomics.

[20]  E. Reed,et al.  Suramin in advanced platinum-resistant ovarian cancer. , 1992, European journal of cancer.

[21]  R. Danesi,et al.  A pilot study of suramin in the treatment of metastatic renal cell carcinoma , 1991, Cancer.

[22]  G. H. Weiss,et al.  Suramin in adrenal cancer: modulation of steroid hormone production, cytotoxicity in vitro, and clinical antitumor effect. , 1990, The Journal of clinical endocrinology and metabolism.

[23]  F. Sola,et al.  Antitumor activity of FCE 26644 a new growth-factor complexing molecule , 2004, Cancer Chemotherapy and Pharmacology.

[24]  S. Dudas,et al.  Identification and localization of the cytokine SDF1 and its receptor, CXC chemokine receptor 4, to regions of necrosis and angiogenesis in human glioblastoma. , 2000, Clinical cancer research : an official journal of the American Association for Cancer Research.

[25]  H. Kleinman,et al.  Vascular endothelial growth factor and basic fibroblast growth factor induce expression of CXCR4 on human endothelial cells: In vivo neovascularization induced by stromal-derived factor-1alpha. , 1999, The American journal of pathology.

[26]  M. Zamai,et al.  Antiangiogenic naphthalene sulfonic distamycin-A derivatives tightly interact with human basic fibroblast growth factor , 1997 .

[27]  O. Sartor,et al.  A phase I/II study of continuous infusion suramin in patients with hormone-refractory prostate cancer : toxicity and response , 1996, Cancer Chemotherapy and Pharmacology.

[28]  M. Ciomei,et al.  FCE 27266, a sulfonic distamycin derivative, inhibits experimental and spontaneous lung and liver metastasis. , 1995, Invasion & metastasis.