Anti-angiogenic effects of pterogynidine alkaloid isolated from Alchornea glandulosa.
BACKGROUND
Angiogenesis, a complex multistep process that comprehends proliferation, migration and anastomosis of endothelial cells (EC), has a major role in the development of pathologic conditions such as inflammatory diseases, tumor growth and metastasis. Brazilian flora, the most diverse in the world, is an interesting spot to prospect for new chemical leads, being an important source of new anticancer drugs. Plant-derived alkaloids have traditionally been of interest due to their pronounced physiological activities. We investigated the anti-angiogenic potential of the naturally occurring guanidine alkaloid pterogynidine (Pt) isolated from the Brazilian plant Alchornea glandulosa. The purpose of this study was to examine which features of the angiogenic process could be disturbed by Pt.


METHODS
Human umbilical vein endothelial cells (HUVEC) were incubated with 8 muM Pt and cell viability, proliferation, apoptosis, invasion and capillary-like structures formation were addressed. Nuclear factor kappaB (NFkappaB), a transcription factor implicated in these processes, was also evaluated in HUVEC incubated with Pt. Quantifications were expressed as mean +/- SD of five independent experiments and one-way analysis of variance (ANOVA) followed by the Dunnet test was used.


RESULTS
A significant decrease in proliferation and invasion capacity and an effective increase in apoptosis as assessed by bromodeoxyuridine (BrdU), double-chamber and terminal transferase dUTP nick end labeling (TUNEL) assay, respectively, have been found. Pt also led to a drastic reduction in the number of capillary-like structures formation when HUVEC were cultured on growth factor reduced-Matrigel (GFR-Matrigel) coated plates. In addition, incubation of HUVEC with Pt resulted in reduced NFkappaB activity.


CONCLUSIONS
These findings emphasize the potential use of Pt against pathological situations where angiogenesis is stimulated as tumor development.
Lopes
Flávia C M
FC
Department of Clinical Analysis, Faculty of Pharmaceutical Sciences of Araraquara, São Paulo State University-UNESP, R, Expedicionários do Brasil, Araraquara, São Paulo, Brazil. fcmlopes@yahoo.com.br
Rocha
Ana
A
Pirraco
Ana
A
Regasini
Luis O
LO
Silva
Dulce H S
DH
Bolzani
Vanderlan S
VS
Azevedo
Isabel
I
Carlos
Iracilda Z
IZ
Soares
Raquel
R
D000470:Alkaloids / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D000704:Analysis of Variance; D020533:Angiogenesis Inhibitors / Q000302:isolation & purification / Q000494:pharmacology*; D000972:Antineoplastic Agents, Phytogenic / Q000302:isolation & purification / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects*; D042783:Endothelial Cells / Q000187:drug effects*; D019665:Euphorbiaceae / Q000737:chemistry*; D006146:Guanidines / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D006801:Humans; D020287:In Situ Nick-End Labeling; D016328:NF-kappa B / Q000037:antagonists & inhibitors; D009361:Neoplasm Invasiveness; D010936:Plant Extracts / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D018515:Plant Leaves; D010946:Plants, Medicinal / Q000737:chemistry; D014471:Umbilical Veins
D000470:Alkaloids; D020533:Angiogenesis Inhibitors; D000972:Antineoplastic Agents, Phytogenic; D006146:Guanidines; D016328:NF-kappa B; D010936:Plant Extracts; C542891:pterogynidine