Purine analogue 6-methylmercaptopurine riboside inhibits early and late phases of the angiogenesis process

Marco Presta, Marco Rusnati, Mirella Belleri, Lucia Morbidelli, Marina Ziche, Domenico Ribatti

Research output: Contribution to journalArticle

Abstract

Angiogenesis has been identified as an important target for antineoplastic therapy. The use of purine analogue antimetabolites in combination chemotherapy of solid tumors has been proposed. To assess the possibility that selected purine analogues may affect tumor neovascularization, 6-methylmercaptopurine riboside (6-MMPR), 6- methylmercaptopurine, 2-aminopurine, and adenosine were evaluated for the capacity to inhibit angiogenesis in vitro and fit vivo. 6-MMPR inhibited fibroblast growth factor-2 (FGF2)-induced proliferation and delayed the repair of mechanically wounded monolayer in endothelial GM 7373 cell cultures. 6-MMPR also inhibited the formation of solid sprouts within fibrin gel by FGF2-treated murine brain microvascular endothelial cells and the formation of capillary-like structures on Matrigel by murine aortic endothelial cells transfected with FGF2 cDNA. 6-MMPR affected FGF2-induced intracellular signaling in murine aortic endothelial cells by inhibiting the phosphorylation of extracellular signal-regulated kinase-2. The other molecules were ineffective in all of the assays. In vivo, 6-MMPR inhibited vascularization in the chick embryo chorioallantoic membrane and prevented blood vessel formation induced by human endometrial adenocarcinoma specimens grafted onto the chorioallantoic membrane. Also, topical administration of 6- MMPR caused the regression of newly formed blood vessels in the rabbit cornea. Thus, 6-MMPR specifically inhibits both the early and the late phases of the angiogenesis process in vitro and exerts a potent anti-angiogenic activity in vivo. These results provide a new rationale for the use of selected purine analogues in combination therapy of solid cancer.

Original languageEnglish
Pages (from-to)2417-2424
Number of pages8
JournalCancer Research
Volume59
Issue number10
Publication statusPublished - May 15 1999

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Methylthioinosine
Fibroblast Growth Factor 2
Chorioallantoic Membrane
Endothelial Cells
Blood Vessels
2-Aminopurine
Topical Administration
Antimetabolites
Neoplasms
Mitogen-Activated Protein Kinase 1
Chick Embryo
Combination Drug Therapy
Fibrin
Antineoplastic Agents
Adenosine
Cornea
purine
Adenocarcinoma
Complementary DNA
Cell Culture Techniques

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Presta, M., Rusnati, M., Belleri, M., Morbidelli, L., Ziche, M., & Ribatti, D. (1999). Purine analogue 6-methylmercaptopurine riboside inhibits early and late phases of the angiogenesis process. Cancer Research, 59(10), 2417-2424.

Purine analogue 6-methylmercaptopurine riboside inhibits early and late phases of the angiogenesis process. / Presta, Marco; Rusnati, Marco; Belleri, Mirella; Morbidelli, Lucia; Ziche, Marina; Ribatti, Domenico.

In: Cancer Research, Vol. 59, No. 10, 15.05.1999, p. 2417-2424.

Research output: Contribution to journalArticle

Presta, M, Rusnati, M, Belleri, M, Morbidelli, L, Ziche, M & Ribatti, D 1999, 'Purine analogue 6-methylmercaptopurine riboside inhibits early and late phases of the angiogenesis process', Cancer Research, vol. 59, no. 10, pp. 2417-2424.
Presta M, Rusnati M, Belleri M, Morbidelli L, Ziche M, Ribatti D. Purine analogue 6-methylmercaptopurine riboside inhibits early and late phases of the angiogenesis process. Cancer Research. 1999 May 15;59(10):2417-2424.
Presta, Marco ; Rusnati, Marco ; Belleri, Mirella ; Morbidelli, Lucia ; Ziche, Marina ; Ribatti, Domenico. / Purine analogue 6-methylmercaptopurine riboside inhibits early and late phases of the angiogenesis process. In: Cancer Research. 1999 ; Vol. 59, No. 10. pp. 2417-2424.
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