title: Panduratin A inhibits the growth of A549 cells through induction of apoptosis and inhibition of NF-kappaB translocation.
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.
authors: Centre of Natural Products & Drug Discovery (CENAR), Department of Pharmacology, Faculty of Medicine, University of Malaya, 50603 Kuala Lumpur, Malaysia. cheahsc@um.edu.my
authors: Shiau-Chuen
authors: SC
authors: Cheah
authors: David R
authors: DR
authors: Appleton
authors: Sui-Ting
authors: ST
authors: Lee
authors: May-Lynn
authors: ML
authors: Lam
authors: A Hamid A
authors: AH
authors: Hadi
authors: Mohd Rais
authors: MR
authors: Mustafa
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D001692:Biological Transport; D002455:Cell Division / Q000187:drug effects*; D002460:Cell Line; D047188:Chalcones / Q000494:pharmacology*; D006801:Humans; D016328:NF-kappa B / Q000378:metabolism*
chemical_list: D047188:Chalcones; D016328:NF-kappa B; C482884:panduratin A