Panduratin A Inhibits the Growth of A549 Cells through Induction of Apoptosis and Inhibition of NF-KappaB Translocation

Molecules

Shiau-Chuen Cheah¹  David R. Appleton²  Sui-Ting Lee¹  May-Lynn Lam¹  A. Hamid A. Hadi³ 

[1] Centre of Natural Products & Drug Discovery (CENAR), Department of Pharmacology, Faculty of Medicine, University of Malaya, 50603 Kuala Lumpur, Malaysia;Centre of Natural Products & Drug Discovery (CENAR), Department of Pharmacology, Faculty of Medicine, University of Malaya, 50603 Kuala Lumpur, Malaysia<;Centre of Natural Products & Drug Discovery (CENAR), Department of Pharmacology, Faculty of Medicine, University of Malaya, 50603 Kuala Lumpur, Malaysia

关键词: Panduratin A;    apoptosis;    High Content Screening;    Real-time Cellular Analyzer;    NF-κB;   

DOI  :  10.3390/molecules16032583

来源: mdpi

【 摘 要 】

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.

【 授权许可】

CC BY   
This is an open access article distributed under the Creative Commons Attribution License (CC BY) which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.