In vitro and in vivo anti-angiogenic activities of Panduratin A.
BACKGROUND
Targeting angiogenesis has emerged as an attractive and promising strategy in anti-cancer therapeutic development. The present study investigates the anti-angiogenic potential of Panduratin A (PA), a natural chalcone isolated from Boesenbergia rotunda by using both in vitro and in vivo assays.


RESULTS
PA exerted selective cytotoxicity on human umbilical vein endothelial cells (HUVECs) with IC(50) value of 6.91 ± 0.85 µM when compared to human normal fibroblast and normal liver epithelial cells. Assessment of the growth kinetics by cell impedance-based Real-Time Cell Analyzer showed that PA induced both cytotoxic and cytostatic effects on HUVECs, depending on the concentration used. Results also showed that PA suppressed VEGF-induced survival and proliferation of HUVECs. Furthermore, endothelial cell migration, invasion, and morphogenesis or tube formation demonstrated significant time- and dose-dependent inhibition by PA. PA also suppressed matrix metalloproteinase-2 (MMP-2) secretion and attenuated its activation to intermediate and active MMP-2. In addition, PA suppressed F-actin stress fiber formation to prevent migration of the endothelial cells. More importantly, anti-angiogenic potential of PA was also evidenced in two in vivo models. PA inhibited neo-vessels formation in murine Matrigel plugs, and angiogenesis in zebrafish embryos.


CONCLUSIONS
Taken together, our study demonstrated the distinctive anti-angiogenic properties of PA, both in vitro and in vivo. This report thus reveals another biological activity of PA in addition to its reported anti-inflammatory and anti-cancer activities, suggestive of PA's potential for development as an anti-angiogenic agent for cancer therapy.
Centre of Natural Products & Drug Discovery, CENAR, Department of Pharmacology, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia.
Siew-Li
SL
Lai
Shiau-Chuen
SC
Cheah
Pooi-Fong
PF
Wong
Suzita Mohd
SM
Noor
Mohd Rais
MR
Mustafa
D020533:Angiogenesis Inhibitors / Q000494:pharmacology*; D000818:Animals; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D047188:Chalcones / Q000494:pharmacology*; D002633:Chemotaxis / Q000187:drug effects; D003094:Collagen / Q000378:metabolism; D003599:Cytoskeleton / Q000187:drug effects / Q000378:metabolism; D054697:Cytostatic Agents / Q000494:pharmacology*; D003603:Cytotoxins / Q000494:pharmacology*; D004338:Drug Combinations; D004789:Enzyme Activation / Q000187:drug effects; D061307:Human Umbilical Vein Endothelial Cells / Q000166:cytology / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D006801:Humans; D007797:Laminin / Q000378:metabolism; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D051379:Mice; D018919:Neovascularization, Physiologic / Q000187:drug effects; D011509:Proteoglycans / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000494:pharmacology; D015027:Zebrafish; D030521:Zingiberaceae / Q000737:chemistry
D020533:Angiogenesis Inhibitors; D047188:Chalcones; D054697:Cytostatic Agents; D003603:Cytotoxins; D004338:Drug Combinations; D007797:Laminin; D011509:Proteoglycans; D042461:Vascular Endothelial Growth Factor A; C059485:matrigel; C482884:panduratin A; D003094:Collagen; D020778:Matrix Metalloproteinase 2