Anti-angiogenic activity of Ipomoea obscura extract and Ipobscurine-A.
OBJECTIVE
Ipomoea obscura (L.) Ker-Gawl, is a medicinal herb with indole alkaloids as an active constituent. In this study, we investigated the anti-angiogenic activity of I. obscura extract and one of its major compounds Ipobscurine-A (IPO-A).


METHODS
In vivo angiogenesis was induced by injecting B16F10 melanoma cells intradermally on the shaven ventral skin of C57BL/6 mice. In vitro experiments were conducted using human umbilical vein endothelial cells.


RESULTS
I. obscura and IPO-A significantly inhibited endothelial cell proliferation, migration, invasion, and tube formation in vitro. Vascular endothelial growth factor (VEGF)-induced sprouting of endothelial cells from rat aorta ex vivo was also inhibited. A marked decrease in the production of matrix metalloproteinases (MMPs) and the expressions of VEGF, cyclooxygenase-2, and nitric oxide synthase by B16F10 cells were observed after the treatment with the extract or IPO-A. Intraperitoneal administration of the extract significantly inhibited B16F10 melanoma cell line-induced neo-vessel formation in C57BL/6 mice in vivo. Analysis of serum cytokine profile clearly showed that extract significantly reduced the elevated levels of pro-inflammatory cytokines such as interleukins (IL)-1β, IL-6, tumor necrosis factor-α, and granulocyte-monocyte colony stimulating factor and the most potent angiogenic factor VEGF in animals. Serum NO level was also found to be significantly lowered by the administration of the extract. Anti-angiogenic factors such as TIMP-1 and IL-2 level were elevated in the extract-treated animals.


CONCLUSIONS
These data clearly demonstrate that I. obscura extract and IPO-A inhibit the tumor-specific angiogenesis by downregulating pro-angiogenic factors such as MMP, VEGF, and pro-inflammatory mediators and upregulating anti-angiogenic factors such as IL-2 and TIMP-1.
Department of Immunology, Amala Cancer Research Centre, Thrissur, Kerala, India.
T P
TP
Hamsa
Girija
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Kuttan
D020533:Angiogenesis Inhibitors / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D000818:Animals; D001011:Aorta / Q000187:drug effects / Q000378:metabolism; D002460:Cell Line; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D051546:Cyclooxygenase 2 / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D061307:Human Umbilical Vein Endothelial Cells / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D026121:Indole Alkaloids / Q000737:chemistry* / Q000302:isolation & purification / Q000494:pharmacology*; D027741:Ipomoea / Q000737:chemistry*; D020782:Matrix Metalloproteinases / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D019001:Nitric Oxide Synthase / Q000378:metabolism; D009573:Nitrites / Q000097:blood; D010936:Plant Extracts / Q000737:chemistry* / Q000302:isolation & purification / Q000494:pharmacology*; D010946:Plants, Medicinal / Q000737:chemistry; D051381:Rats; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
D020533:Angiogenesis Inhibitors; D016207:Cytokines; D026121:Indole Alkaloids; D009573:Nitrites; D010936:Plant Extracts; D019715:Tissue Inhibitor of Metalloproteinase-1; D042461:Vascular Endothelial Growth Factor A; D019001:Nitric Oxide Synthase; D051546:Cyclooxygenase 2; D020782:Matrix Metalloproteinases