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Polyphenols in Ilex latifolia Thunb. inhibit human lung cancer cell line A549 by regulation of the PI3K-Akt signaling pathway

BACKGROUND: The leaves of the plant Ilex latifolia Thunb. can be made into Kuding tea, which is a drink rich in polyphenols. This study aimed to observe the effect of Ilex latifolia Thunb. polyphenols (ILTPs) on human lung cancer cell line A549 (A549 cells) by regulating the phosphatidylinositol 3-k...

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Autores principales: Chen, Jing, Du, Yesheng, Long, Yanyan, Tao, Dan, Hu, Mengyu, Jiang, Yong, Wan, Yue, Yang, Dingyi
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8943935/
https://www.ncbi.nlm.nih.gov/pubmed/35321703
http://dx.doi.org/10.1186/s12906-022-03568-3
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author Chen, Jing
Du, Yesheng
Long, Yanyan
Tao, Dan
Hu, Mengyu
Jiang, Yong
Wan, Yue
Yang, Dingyi
author_facet Chen, Jing
Du, Yesheng
Long, Yanyan
Tao, Dan
Hu, Mengyu
Jiang, Yong
Wan, Yue
Yang, Dingyi
author_sort Chen, Jing
collection PubMed
description BACKGROUND: The leaves of the plant Ilex latifolia Thunb. can be made into Kuding tea, which is a drink rich in polyphenols. This study aimed to observe the effect of Ilex latifolia Thunb. polyphenols (ILTPs) on human lung cancer cell line A549 (A549 cells) by regulating the phosphatidylinositol 3-kinase/protein kinase B (PI3K/Akt) signaling pathway. METHODS: In vitro cultured cells were treated with ILTPs; the proliferation of A549 cells and BEAS-2B human normal lung epithelial cells (Beas-2B cells) was observed using the 3-(4,5-dimethylazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, and the survival status of A549 cells was observed by fluorescence staining. The expression of A549 cells was observed by quantitative polymerase chain reaction (qPCR) assay and Western blot analysis, while the compound composition of ILTPs was detected using high-performance liquid chromatography (HPLC). RESULTS: The experimental results showed that the proliferation of Beas-2B cells was unaffected by treatment with 0–500 μg/mL of ILTPs, whereas the decreased proliferation of A549 cells was observed with the increasing concentrations of ILTPs. Additionally, ILTPs elevated the levels of lactate dehydrogenase (LDH) and reactive oxygen species (ROS) and promoted apoptosis in A549 cells. The results of qPCR experiments showed that ILTPs upregulated caspase-9 mRNA expression and downregulated phosphatidylinositol 3-kinase (PI3K), protein kinase B (Akt), mammalian target of rapamycin (mTOR), B-cell lymphoma-2 (Bcl-2), nuclear factor-κB (NF-κB), vascular endothelial growth factor (VEGF), hypoxia-inducible factor-1 alpha (HIF-1α), and cyclooxygenase-2 (COX-2) expression in A549 cells. The Western blot analysis results also showed that ILTPs could reduce the protein expression of PI3K and Akt. The HPLC results showed that the main compounds present in the ILTPs were rutin, kaempferol, isochlorogenic acid A, isochlorogenic acid B, and isochlorogenic acid C. CONCLUSIONS: Thus, this study indicated that the polyphenols of I. latifolia act as a class of natural functional food materials that potently suppress cancer by exerting their inhibitory effects on A549 cell proliferation through five key polyphenolic compounds. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12906-022-03568-3.
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spelling pubmed-89439352022-03-25 Polyphenols in Ilex latifolia Thunb. inhibit human lung cancer cell line A549 by regulation of the PI3K-Akt signaling pathway Chen, Jing Du, Yesheng Long, Yanyan Tao, Dan Hu, Mengyu Jiang, Yong Wan, Yue Yang, Dingyi BMC Complement Med Ther Research Article BACKGROUND: The leaves of the plant Ilex latifolia Thunb. can be made into Kuding tea, which is a drink rich in polyphenols. This study aimed to observe the effect of Ilex latifolia Thunb. polyphenols (ILTPs) on human lung cancer cell line A549 (A549 cells) by regulating the phosphatidylinositol 3-kinase/protein kinase B (PI3K/Akt) signaling pathway. METHODS: In vitro cultured cells were treated with ILTPs; the proliferation of A549 cells and BEAS-2B human normal lung epithelial cells (Beas-2B cells) was observed using the 3-(4,5-dimethylazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, and the survival status of A549 cells was observed by fluorescence staining. The expression of A549 cells was observed by quantitative polymerase chain reaction (qPCR) assay and Western blot analysis, while the compound composition of ILTPs was detected using high-performance liquid chromatography (HPLC). RESULTS: The experimental results showed that the proliferation of Beas-2B cells was unaffected by treatment with 0–500 μg/mL of ILTPs, whereas the decreased proliferation of A549 cells was observed with the increasing concentrations of ILTPs. Additionally, ILTPs elevated the levels of lactate dehydrogenase (LDH) and reactive oxygen species (ROS) and promoted apoptosis in A549 cells. The results of qPCR experiments showed that ILTPs upregulated caspase-9 mRNA expression and downregulated phosphatidylinositol 3-kinase (PI3K), protein kinase B (Akt), mammalian target of rapamycin (mTOR), B-cell lymphoma-2 (Bcl-2), nuclear factor-κB (NF-κB), vascular endothelial growth factor (VEGF), hypoxia-inducible factor-1 alpha (HIF-1α), and cyclooxygenase-2 (COX-2) expression in A549 cells. The Western blot analysis results also showed that ILTPs could reduce the protein expression of PI3K and Akt. The HPLC results showed that the main compounds present in the ILTPs were rutin, kaempferol, isochlorogenic acid A, isochlorogenic acid B, and isochlorogenic acid C. CONCLUSIONS: Thus, this study indicated that the polyphenols of I. latifolia act as a class of natural functional food materials that potently suppress cancer by exerting their inhibitory effects on A549 cell proliferation through five key polyphenolic compounds. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12906-022-03568-3. BioMed Central 2022-03-23 /pmc/articles/PMC8943935/ /pubmed/35321703 http://dx.doi.org/10.1186/s12906-022-03568-3 Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
spellingShingle Research Article
Chen, Jing
Du, Yesheng
Long, Yanyan
Tao, Dan
Hu, Mengyu
Jiang, Yong
Wan, Yue
Yang, Dingyi
Polyphenols in Ilex latifolia Thunb. inhibit human lung cancer cell line A549 by regulation of the PI3K-Akt signaling pathway
title Polyphenols in Ilex latifolia Thunb. inhibit human lung cancer cell line A549 by regulation of the PI3K-Akt signaling pathway
title_full Polyphenols in Ilex latifolia Thunb. inhibit human lung cancer cell line A549 by regulation of the PI3K-Akt signaling pathway
title_fullStr Polyphenols in Ilex latifolia Thunb. inhibit human lung cancer cell line A549 by regulation of the PI3K-Akt signaling pathway
title_full_unstemmed Polyphenols in Ilex latifolia Thunb. inhibit human lung cancer cell line A549 by regulation of the PI3K-Akt signaling pathway
title_short Polyphenols in Ilex latifolia Thunb. inhibit human lung cancer cell line A549 by regulation of the PI3K-Akt signaling pathway
title_sort polyphenols in ilex latifolia thunb. inhibit human lung cancer cell line a549 by regulation of the pi3k-akt signaling pathway
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8943935/
https://www.ncbi.nlm.nih.gov/pubmed/35321703
http://dx.doi.org/10.1186/s12906-022-03568-3
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