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Activity and mechanism of flavokawain A in inhibiting P-glycoprotein expression in paclitaxel resistance of lung cancer
Lung cancer is one of the most common cancers, which is the leading cause of cancer-related death among various cancers worldwide. Flavokawain A (FKA), a chalcone found in the kava plant, exerts potent anticancer activity. However, the activity and mechanisms of FKA in inhibiting the viability of pa...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
D.A. Spandidos
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6923923/ https://www.ncbi.nlm.nih.gov/pubmed/31897150 http://dx.doi.org/10.3892/ol.2019.11069 |
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author | Li, Juan Zheng, Lei Yan, Mi Wu, Jing Liu, Yongqing Tian, Xiaona Jiang, Wen Zhang, Lu Wang, Rongmei |
author_facet | Li, Juan Zheng, Lei Yan, Mi Wu, Jing Liu, Yongqing Tian, Xiaona Jiang, Wen Zhang, Lu Wang, Rongmei |
author_sort | Li, Juan |
collection | PubMed |
description | Lung cancer is one of the most common cancers, which is the leading cause of cancer-related death among various cancers worldwide. Flavokawain A (FKA), a chalcone found in the kava plant, exerts potent anticancer activity. However, the activity and mechanisms of FKA in inhibiting the viability of paclitaxel (PTX)-resistant lung cancer A549 (A549/T) have not been investigated. In the present study, the effect of FKA on the viability of A549/T and hepatotoxicity in normal liver epithelial cells was detected by Cell Counting Kit-8 assay. Flow cytometry, western blot analysis and Annexin V-FITC/PI apoptosis detection kit were used to assess cell apoptosis. The effect of FKA on permeability-glycoprotein (P-gp) expression was measured by reverse transcription-PCR and western blot analysis. The results indicated that FKA dose-dependently inhibited cell proliferation and induced cell apoptosis in PTX-resistant A549/T cells, with an IC(50) value of ~21 µM, while the IC(50) value of A549/T cells to PTX was 34.64 µM. FKA had no hepatic toxicity in liver epithelial cells. P-gp, which contributes to the chemoresistant phenotype, was not expressed in A549 cells but was remarkably enhanced in A549/T cells. FKA (30 µM) decreased P-gp protein expression at 24 h by 3-fold. Furthermore, FKA downregulated P-gp expression by blocking the PI3K/Akt pathway. These findings suggest FKA as a potential candidate for the treatment of PTX-resistant lung cancer. |
format | Online Article Text |
id | pubmed-6923923 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | D.A. Spandidos |
record_format | MEDLINE/PubMed |
spelling | pubmed-69239232020-01-02 Activity and mechanism of flavokawain A in inhibiting P-glycoprotein expression in paclitaxel resistance of lung cancer Li, Juan Zheng, Lei Yan, Mi Wu, Jing Liu, Yongqing Tian, Xiaona Jiang, Wen Zhang, Lu Wang, Rongmei Oncol Lett Articles Lung cancer is one of the most common cancers, which is the leading cause of cancer-related death among various cancers worldwide. Flavokawain A (FKA), a chalcone found in the kava plant, exerts potent anticancer activity. However, the activity and mechanisms of FKA in inhibiting the viability of paclitaxel (PTX)-resistant lung cancer A549 (A549/T) have not been investigated. In the present study, the effect of FKA on the viability of A549/T and hepatotoxicity in normal liver epithelial cells was detected by Cell Counting Kit-8 assay. Flow cytometry, western blot analysis and Annexin V-FITC/PI apoptosis detection kit were used to assess cell apoptosis. The effect of FKA on permeability-glycoprotein (P-gp) expression was measured by reverse transcription-PCR and western blot analysis. The results indicated that FKA dose-dependently inhibited cell proliferation and induced cell apoptosis in PTX-resistant A549/T cells, with an IC(50) value of ~21 µM, while the IC(50) value of A549/T cells to PTX was 34.64 µM. FKA had no hepatic toxicity in liver epithelial cells. P-gp, which contributes to the chemoresistant phenotype, was not expressed in A549 cells but was remarkably enhanced in A549/T cells. FKA (30 µM) decreased P-gp protein expression at 24 h by 3-fold. Furthermore, FKA downregulated P-gp expression by blocking the PI3K/Akt pathway. These findings suggest FKA as a potential candidate for the treatment of PTX-resistant lung cancer. D.A. Spandidos 2020-01 2019-11-08 /pmc/articles/PMC6923923/ /pubmed/31897150 http://dx.doi.org/10.3892/ol.2019.11069 Text en Copyright: © Li et al. This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License (https://creativecommons.org/licenses/by-nc-nd/4.0/) , which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made. |
spellingShingle | Articles Li, Juan Zheng, Lei Yan, Mi Wu, Jing Liu, Yongqing Tian, Xiaona Jiang, Wen Zhang, Lu Wang, Rongmei Activity and mechanism of flavokawain A in inhibiting P-glycoprotein expression in paclitaxel resistance of lung cancer |
title | Activity and mechanism of flavokawain A in inhibiting P-glycoprotein expression in paclitaxel resistance of lung cancer |
title_full | Activity and mechanism of flavokawain A in inhibiting P-glycoprotein expression in paclitaxel resistance of lung cancer |
title_fullStr | Activity and mechanism of flavokawain A in inhibiting P-glycoprotein expression in paclitaxel resistance of lung cancer |
title_full_unstemmed | Activity and mechanism of flavokawain A in inhibiting P-glycoprotein expression in paclitaxel resistance of lung cancer |
title_short | Activity and mechanism of flavokawain A in inhibiting P-glycoprotein expression in paclitaxel resistance of lung cancer |
title_sort | activity and mechanism of flavokawain a in inhibiting p-glycoprotein expression in paclitaxel resistance of lung cancer |
topic | Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6923923/ https://www.ncbi.nlm.nih.gov/pubmed/31897150 http://dx.doi.org/10.3892/ol.2019.11069 |
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