Piper longum inhibits VEGF and proinflammatory cytokines and tumor-induced angiogenesis in C57BL/6 mice. Int Immunopharmacol 2006 May;6(5):733-41
Date
03/21/2006Pubmed ID
16546703DOI
10.1016/j.intimp.2005.10.013Scopus ID
2-s2.0-33645021929 (requires institutional sign-in at Scopus site) 35 CitationsAbstract
The antiangiogenic activity of Piper longum was studied using in vivo as well as in vitro models. In vivo, antiangiogenic activity was studied using B16F-10 melanoma cell-induced capillary formation in C57BL/6 mice. Intraperitoneal administration of the extract (10 mg/dose/animal) significantly inhibited (50.6%) the number of tumor-directed capillaries induced by injecting B16F-10 melanoma cells on the ventral side of C57BL/6 mice. The cytokine profile in the serum of these animals showed a drastically increased level of proinflammatory cytokines such as IL-1beta, IL-6, TNF-alpha, GM-CSF and the direct endothelial cell proliferating agent, VEGF. Administration of the methanolic extract of P. longum could differentially regulate the level of these cytokines. The level of IL-2 and tissue inhibitor of metalloprotease-1 (TIMP-1) was increased significantly when the angiogenesis-induced animals were treated with the extract. The extract of P. longum at non-toxic concentrations (10 microg/ml, 5 microg/ml, 1 microg/ml) inhibited the VEGF-induced vessel sprouting in rat aortic ring assay. Moreover, P. longum was able to inhibit the VEGF-induced proliferation, cell migration and capillary-like tube formation of primary cultured human endothelial cells. Hence, the observed antiangiogenic activity of the plant P. longum is related to the regulation of these cytokines and growth factors in angiogenesis-induced animals.
Author List
Sunila ES, Kuttan GAuthor
Sunila Pradeep PhD Associate Professor in the Obstetrics and Gynecology department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
Angiogenesis InhibitorsAnimals
Aorta
Cell Movement
Cell Proliferation
Cytokines
Endothelial Cells
Gene Expression Regulation, Neoplastic
Humans
In Vitro Techniques
Male
Melanoma, Experimental
Mice
Mice, Inbred C57BL
Neovascularization, Pathologic
Piper
Plant Extracts
RNA, Messenger
Rats
Rats, Sprague-Dawley
Vascular Endothelial Growth Factors
