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Andrographolide Suppresses MV4-11 Cell Proliferation through the Inhibition of FLT3 Signaling, Fatty Acid Synthesis and Cellular Iron Uptake

Background: Andrographolide (ADR), the main active component of Andrographis paniculata, displays anticancer activity in various cancer cell lines, among which leukemia cell lines exhibit the highest sensitivity to ADR. In particular, ADR was also reported to have reduced drug resistance in multidru...

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Autores principales: Chen, Xiao, Zhang, Jianbin, Yuan, Lixia, Lay, Yifei, Wong, Yin Kwan, Lim, Teck Kwang, Ong, Chye Sun, Lin, Qingsong, Wang, Jigang, Hua, Zichun
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6151431/
https://www.ncbi.nlm.nih.gov/pubmed/28858244
http://dx.doi.org/10.3390/molecules22091444
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author Chen, Xiao
Zhang, Jianbin
Yuan, Lixia
Lay, Yifei
Wong, Yin Kwan
Lim, Teck Kwang
Ong, Chye Sun
Lin, Qingsong
Wang, Jigang
Hua, Zichun
author_facet Chen, Xiao
Zhang, Jianbin
Yuan, Lixia
Lay, Yifei
Wong, Yin Kwan
Lim, Teck Kwang
Ong, Chye Sun
Lin, Qingsong
Wang, Jigang
Hua, Zichun
author_sort Chen, Xiao
collection PubMed
description Background: Andrographolide (ADR), the main active component of Andrographis paniculata, displays anticancer activity in various cancer cell lines, among which leukemia cell lines exhibit the highest sensitivity to ADR. In particular, ADR was also reported to have reduced drug resistance in multidrug resistant cell lines. However, the mechanism of action (MOA) of ADR’s anticancer and anti-drug-resistance activities remain elusive. Methods: In this study, we used the MV4-11 cell line, a FLT3 positive acute myeloid leukemia (AML) cell line that displays multidrug resistance, as our experimental system. We first evaluated the effect of ADR on MV4-11 cell proliferation. Then, a quantitative proteomics approach was applied to identify differentially expressed proteins in ADR-treated MV4-11 cells. Finally, cellular processes and signal pathways affected by ADR in MV4-11 cell were predicted with proteomic analysis and validated with in vitro assays. Results: ADR inhibits MV4-11 cell proliferation in a dose- and time-dependent manner. With a proteomic approach, we discovered that ADR inhibited fatty acid synthesis, cellular iron uptake and FLT3 signaling pathway in MV4-11 cells. Conclusions: ADR inhibits MV4-11 cell proliferation through inhibition of fatty acid synthesis, iron uptake and protein synthesis. Furthermore, ADR reduces drug resistance by blocking FLT3 signaling.
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spelling pubmed-61514312018-11-13 Andrographolide Suppresses MV4-11 Cell Proliferation through the Inhibition of FLT3 Signaling, Fatty Acid Synthesis and Cellular Iron Uptake Chen, Xiao Zhang, Jianbin Yuan, Lixia Lay, Yifei Wong, Yin Kwan Lim, Teck Kwang Ong, Chye Sun Lin, Qingsong Wang, Jigang Hua, Zichun Molecules Article Background: Andrographolide (ADR), the main active component of Andrographis paniculata, displays anticancer activity in various cancer cell lines, among which leukemia cell lines exhibit the highest sensitivity to ADR. In particular, ADR was also reported to have reduced drug resistance in multidrug resistant cell lines. However, the mechanism of action (MOA) of ADR’s anticancer and anti-drug-resistance activities remain elusive. Methods: In this study, we used the MV4-11 cell line, a FLT3 positive acute myeloid leukemia (AML) cell line that displays multidrug resistance, as our experimental system. We first evaluated the effect of ADR on MV4-11 cell proliferation. Then, a quantitative proteomics approach was applied to identify differentially expressed proteins in ADR-treated MV4-11 cells. Finally, cellular processes and signal pathways affected by ADR in MV4-11 cell were predicted with proteomic analysis and validated with in vitro assays. Results: ADR inhibits MV4-11 cell proliferation in a dose- and time-dependent manner. With a proteomic approach, we discovered that ADR inhibited fatty acid synthesis, cellular iron uptake and FLT3 signaling pathway in MV4-11 cells. Conclusions: ADR inhibits MV4-11 cell proliferation through inhibition of fatty acid synthesis, iron uptake and protein synthesis. Furthermore, ADR reduces drug resistance by blocking FLT3 signaling. MDPI 2017-08-31 /pmc/articles/PMC6151431/ /pubmed/28858244 http://dx.doi.org/10.3390/molecules22091444 Text en © 2017 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Chen, Xiao
Zhang, Jianbin
Yuan, Lixia
Lay, Yifei
Wong, Yin Kwan
Lim, Teck Kwang
Ong, Chye Sun
Lin, Qingsong
Wang, Jigang
Hua, Zichun
Andrographolide Suppresses MV4-11 Cell Proliferation through the Inhibition of FLT3 Signaling, Fatty Acid Synthesis and Cellular Iron Uptake
title Andrographolide Suppresses MV4-11 Cell Proliferation through the Inhibition of FLT3 Signaling, Fatty Acid Synthesis and Cellular Iron Uptake
title_full Andrographolide Suppresses MV4-11 Cell Proliferation through the Inhibition of FLT3 Signaling, Fatty Acid Synthesis and Cellular Iron Uptake
title_fullStr Andrographolide Suppresses MV4-11 Cell Proliferation through the Inhibition of FLT3 Signaling, Fatty Acid Synthesis and Cellular Iron Uptake
title_full_unstemmed Andrographolide Suppresses MV4-11 Cell Proliferation through the Inhibition of FLT3 Signaling, Fatty Acid Synthesis and Cellular Iron Uptake
title_short Andrographolide Suppresses MV4-11 Cell Proliferation through the Inhibition of FLT3 Signaling, Fatty Acid Synthesis and Cellular Iron Uptake
title_sort andrographolide suppresses mv4-11 cell proliferation through the inhibition of flt3 signaling, fatty acid synthesis and cellular iron uptake
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6151431/
https://www.ncbi.nlm.nih.gov/pubmed/28858244
http://dx.doi.org/10.3390/molecules22091444
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