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Panduratin A Inhibits the Growth of A549 Cells through Induction of Apoptosis and Inhibition of NF-KappaB Translocation
Centre of Natural Products & Drug Discovery (CENAR), Department of Pharmacology, Faculty of Medicine, University of Malaya, 50603 Kuala Lumpur, Malaysia
Sime Darby Technology Centre, 1st Floor, Block B, UPM-MTDC Technology Centre III, UPM, Serdang 43400, Selangor, Malaysia
Cancer Research Initiatives Foundation (CARIF), 2nd Floor, Outpatient Centre, Sime Darby Medical Centre, 47500 Subang Jaya, Selangor Darul Ehsan, Malaysia
Centre of Natural Products & Drug Discovery (CENAR), Department of Chemistry, Faculty of Science, University of Malaya, 50603 Kuala Lumpur, Malaysia
* Author to whom correspondence should be addressed.
Received: 23 February 2011; in revised form: 3 March 2011 / Accepted: 11 March 2011 / Published: 21 March 2011
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 factor-alpha (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.
Keywords: Panduratin A; apoptosis; High Content Screening; Real-time Cellular Analyzer; NF-κB
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Cheah, S.-C.; Appleton, D.R.; Lee, S.-T.; Lam, M.-L.; Hadi, A.H.A.; Mustafa, M.R. Panduratin A Inhibits the Growth of A549 Cells through Induction of Apoptosis and Inhibition of NF-KappaB Translocation. Molecules 2011, 16, 2583-2598.
Cheah S-C, Appleton DR, Lee S-T, Lam M-L, Hadi AHA, Mustafa MR. Panduratin A Inhibits the Growth of A549 Cells through Induction of Apoptosis and Inhibition of NF-KappaB Translocation. Molecules. 2011; 16(3):2583-2598.
Cheah, Shiau-Chuen; Appleton, David R.; Lee, Sui-Ting; Lam, May-Lynn; Hadi, A. Hamid A.; Mustafa, Mohd. Rais. 2011. "Panduratin A Inhibits the Growth of A549 Cells through Induction of Apoptosis and Inhibition of NF-KappaB Translocation." Molecules 16, no. 3: 2583-2598.