Panduratin a inhibits the growth of A549 Cells through induction of apoptosis and inhibition of NF-KappaB translocation

Cheah, S.C.; Appleton, D.R.; Lee, S.T.; Lam, M.L.; Hadi, A.H.A.; Mustafa, M.R. (2011) Panduratin a inhibits the growth of A549 Cells through induction of apoptosis and inhibition of NF-KappaB translocation. Molecules, 16 (3). pp. 2583-2598.

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    Abstract

    In the present study we investigated the effects of panduratin A, isolated from Boesenbergia rotunda, on proliferation and apoptosis in A549 human non-small cell lung cancer cells. Cell proliferation and induction of apoptosis was determined by the real-time cellular analyzer (RTCA), MTT assay and High Content Screening (HCS). The RTCA assay indicated that panduratin A exhibited cytotoxicity, with an IC50 value of 4.4 µg/mL 10.8 µM). Panduratin A arrested cancer cells labeled with bromodeoxyuridine (BrdU) and phospho-Histone H3 in the mitotic phase. The cytotoxic effects of panduratin A were found to be accompanied by a dose-dependent induction of apoptosis, as assessed by DNA condensation, nuclear morphology and intensity, cell permeability, mitochondrial mass/potential, F-actin and cytochrome c. In addition, treatment with an apoptosis-inducing concentration of panduratin A resulted in significant inhibition of Nuclear Factor-kappa Beta (NF-κB) translocation from cytoplasm to nuclei activated by tumor necrosis factoralpha (TNF-α), as illustrated by the HCS assay. Our study provides evidence for cell growth inhibition and induction of apoptosis by panduratin A in the A549 cell line,suggesting its therapeutic potential as an NF-κB inhibitor.

    Item Type: Article
    Creators:
    1. Cheah, S.C.
    2. Appleton, D.R.
    3. Lee, S.T.
    4. Lam, M.L.
    5. Hadi, A.H.A.
    6. Mustafa, M.R.
    Journal or Publication Title: Molecules
    Additional Information: Centre of Natural Products & Drug Discovery (CENAR), Department of Pharmacology, Faculty of Medicine, University of Malaya, 50603 Kuala Lumpur, Malaysia; E-Mails: drappleton@hotmail.com (D.R.A.); suiting87@siswa.um.edu.my (S.T.L.);
    Uncontrolled Keywords: Panduratin A, Apoptosis, High Content Screening, Real-time Cellular Analyzer, NF-κB
    Subjects: Q Science > QD Chemistry
    R Medicine
    Divisions: UNSPECIFIED
    Depositing User: Ms Haslinda Lahuddin
    Date Deposited: 17 Jan 2012 14:26
    Last Modified: 11 Dec 2013 15:11
    URI: http://eprints.um.edu.my/id/eprint/2457

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