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Panduratin A, a Possible Inhibitor in Metastasized A549 Cells through Inhibition of NF-Kappa B Translocation and Chemoinvasion
In the present study, we investigated the effects of panduratin A (PA), isolated from Boesenbergia rotunda, on apoptosis and chemoinvasion in A549 human non-small cell lung cancer cells. Activation of the executioner procaspase-3 by PA was found to be dose-dependent. Caspase-3 activity was significa...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2013
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6270481/ https://www.ncbi.nlm.nih.gov/pubmed/23887718 http://dx.doi.org/10.3390/molecules18088764 |
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author | Cheah, Shiau-Chuen Lai, Siew-Li Lee, Sui-Ting Hadi, A. Hamid A. Mustafa, Mohd. Rais |
author_facet | Cheah, Shiau-Chuen Lai, Siew-Li Lee, Sui-Ting Hadi, A. Hamid A. Mustafa, Mohd. Rais |
author_sort | Cheah, Shiau-Chuen |
collection | PubMed |
description | In the present study, we investigated the effects of panduratin A (PA), isolated from Boesenbergia rotunda, on apoptosis and chemoinvasion in A549 human non-small cell lung cancer cells. Activation of the executioner procaspase-3 by PA was found to be dose-dependent. Caspase-3 activity was significantly elevated at the 5 µg/mL level of PA treatment and progressed to a maximal level. However, no significant elevated level was detected on procaspase-8. These findings suggest that PA activated caspase-3 but not caspase-8. Numerous nuclei of PA treated A549 cells stained brightly by anti-cleaved PARP antibody through High Content Screening. This result further confirmed that PA induced apoptotic cell death was mediated through activation of caspase-3 and eventually led to PARP cleavage. Treatment of A549 cells with PA resulted in a strong inhibition of NF-κB activation, which was consistent with a decrease in nuclear levels of NF-κB/p65 and NF-κB/p50 and the elevation of p53 and p21. Besides that, we also showed that PA significantly inhibited the invasion of A549 cells in a dose-dependent manner through reducing the secretion of MMP-2 of A549 cells gelatin zymography assay. Our findings not only provide the effects of PA, but may also be important in the design of therapeutic protocols that involve targeting of either p53 or NF-κB. |
format | Online Article Text |
id | pubmed-6270481 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2013 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-62704812018-12-18 Panduratin A, a Possible Inhibitor in Metastasized A549 Cells through Inhibition of NF-Kappa B Translocation and Chemoinvasion Cheah, Shiau-Chuen Lai, Siew-Li Lee, Sui-Ting Hadi, A. Hamid A. Mustafa, Mohd. Rais Molecules Article In the present study, we investigated the effects of panduratin A (PA), isolated from Boesenbergia rotunda, on apoptosis and chemoinvasion in A549 human non-small cell lung cancer cells. Activation of the executioner procaspase-3 by PA was found to be dose-dependent. Caspase-3 activity was significantly elevated at the 5 µg/mL level of PA treatment and progressed to a maximal level. However, no significant elevated level was detected on procaspase-8. These findings suggest that PA activated caspase-3 but not caspase-8. Numerous nuclei of PA treated A549 cells stained brightly by anti-cleaved PARP antibody through High Content Screening. This result further confirmed that PA induced apoptotic cell death was mediated through activation of caspase-3 and eventually led to PARP cleavage. Treatment of A549 cells with PA resulted in a strong inhibition of NF-κB activation, which was consistent with a decrease in nuclear levels of NF-κB/p65 and NF-κB/p50 and the elevation of p53 and p21. Besides that, we also showed that PA significantly inhibited the invasion of A549 cells in a dose-dependent manner through reducing the secretion of MMP-2 of A549 cells gelatin zymography assay. Our findings not only provide the effects of PA, but may also be important in the design of therapeutic protocols that involve targeting of either p53 or NF-κB. MDPI 2013-07-24 /pmc/articles/PMC6270481/ /pubmed/23887718 http://dx.doi.org/10.3390/molecules18088764 Text en © 2013 by the authors; licensee MDPI, Basel, Switzerland. http://creativecommons.org/licenses/by/3.0/ This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution license (http://creativecommons.org/licenses/by/3.0/). |
spellingShingle | Article Cheah, Shiau-Chuen Lai, Siew-Li Lee, Sui-Ting Hadi, A. Hamid A. Mustafa, Mohd. Rais Panduratin A, a Possible Inhibitor in Metastasized A549 Cells through Inhibition of NF-Kappa B Translocation and Chemoinvasion |
title | Panduratin A, a Possible Inhibitor in Metastasized A549 Cells through Inhibition of NF-Kappa B Translocation and Chemoinvasion |
title_full | Panduratin A, a Possible Inhibitor in Metastasized A549 Cells through Inhibition of NF-Kappa B Translocation and Chemoinvasion |
title_fullStr | Panduratin A, a Possible Inhibitor in Metastasized A549 Cells through Inhibition of NF-Kappa B Translocation and Chemoinvasion |
title_full_unstemmed | Panduratin A, a Possible Inhibitor in Metastasized A549 Cells through Inhibition of NF-Kappa B Translocation and Chemoinvasion |
title_short | Panduratin A, a Possible Inhibitor in Metastasized A549 Cells through Inhibition of NF-Kappa B Translocation and Chemoinvasion |
title_sort | panduratin a, a possible inhibitor in metastasized a549 cells through inhibition of nf-kappa b translocation and chemoinvasion |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6270481/ https://www.ncbi.nlm.nih.gov/pubmed/23887718 http://dx.doi.org/10.3390/molecules18088764 |
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