In vitro and in vivo anti-angiogenic activities of panduratin a.

Lai, S.L.; Cheah, S.C.; Wong, P.F.; Noor, S.M.; Mustafa, M.R. (2012) In vitro and in vivo anti-angiogenic activities of panduratin a. PLoS One, 7 (5).

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    Abstract

    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. METHODOLOGY/PRINCIPAL FINDINGS: 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/SIGNIFICANCE: 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.

    Item Type: Article
    Creators:
    1. Lai, S.L.
    2. Cheah, S.C.
    3. Wong, P.F.
    4. Noor, S.M.
    5. Mustafa, M.R.
    Journal or Publication Title: PLoS One
    Additional Information: Centre of Natural Products & Drug Discovery (CENAR), Department of Pharmacology, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia, and Department of Molecular Medicine, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia
    Uncontrolled Keywords: Molecular Medicine; Pharmacology
    Subjects: R Medicine
    Divisions: UNSPECIFIED
    Depositing User: Mr. Faizal Hamzah
    Date Deposited: 15 Jun 2012 10:03
    Last Modified: 11 Dec 2013 15:13
    URI: http://eprints.um.edu.my/id/eprint/3313

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