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A novel lupene derivative from Thymus capitatus possesses an apoptosis-inducing effect via Let-7 miRNA/Cyclin D1/VEGF cascade in the A549 cell line

Non-small-cell lung carcinoma (NSCLC) is a type of epithelial lung cancer accounting for about 85% of all lung cancers. In our research, a novel lupene derivative namely acetoxy-lup-5(6), 20(29)-diene (ALUP), as well as two known triterpenes; lupeol (LUP) and betulinic acid (BA) were isolated throug...

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Autores principales: Aborehab, Nora M., Salama, Maha M., Ezzat, Shahira M.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10577955/
https://www.ncbi.nlm.nih.gov/pubmed/37845669
http://dx.doi.org/10.1186/s12906-023-04201-7
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author Aborehab, Nora M.
Salama, Maha M.
Ezzat, Shahira M.
author_facet Aborehab, Nora M.
Salama, Maha M.
Ezzat, Shahira M.
author_sort Aborehab, Nora M.
collection PubMed
description Non-small-cell lung carcinoma (NSCLC) is a type of epithelial lung cancer accounting for about 85% of all lung cancers. In our research, a novel lupene derivative namely acetoxy-lup-5(6), 20(29)-diene (ALUP), as well as two known triterpenes; lupeol (LUP) and betulinic acid (BA) were isolated through the chromatographic purification of the 95% ethanolic extract of Thymus capitatus. Identification of the compounds was carried out by physicochemical properties as well as spectral 1D and 2D NMR analysis. The anti-cancer activity of the three triterpenes was assessed on non-small cell lung cancer cell line; A549 using MTT assay and cell cycle analysis using annexin V/propidium iodide. The molecular mechanism underlying anti-apoptotic effects was determined by analyzing Let-7 miRNA and miRNA-21 expression, the mRNA gene expression level of Bax, CASP-8, CD95, Bcl2, KRAS, VEGF, Cyclin D1 using qRT-PCR. Our results revealed that the three isolated compounds ALUP, LUP, and BA caused cell cycle arrest at the G2/M phase with an increase in the apoptosis which may be attributed to their significant effect on raising Bax, CASP-8, and CD95 and reducing the mRNA expression levels of Bcl-2, KRAS, VEGF, and Cyclin D1 compared to control cells. RT-PCR results showed that the ALUP, LUP, and BA significantly downregulated miRNA-21 expression. Meanwhile, the three compounds caused significant overexpression of Let-7 miRNA. This is the first report on the anti-cancer activity of acetoxy-lup-5(6), 20(29)-diene (ALUP) in reducing the proliferation and differentiation of the A549 cell line through inducing apoptosis. Finally, by targeting the Let-7 miRNA/Cyclin D1/VEGF cascade, acetoxy-lup-5(6), 20(29)-diene could be a potential therapeutic agent for lung cancer. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12906-023-04201-7.
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spelling pubmed-105779552023-10-17 A novel lupene derivative from Thymus capitatus possesses an apoptosis-inducing effect via Let-7 miRNA/Cyclin D1/VEGF cascade in the A549 cell line Aborehab, Nora M. Salama, Maha M. Ezzat, Shahira M. BMC Complement Med Ther Research Non-small-cell lung carcinoma (NSCLC) is a type of epithelial lung cancer accounting for about 85% of all lung cancers. In our research, a novel lupene derivative namely acetoxy-lup-5(6), 20(29)-diene (ALUP), as well as two known triterpenes; lupeol (LUP) and betulinic acid (BA) were isolated through the chromatographic purification of the 95% ethanolic extract of Thymus capitatus. Identification of the compounds was carried out by physicochemical properties as well as spectral 1D and 2D NMR analysis. The anti-cancer activity of the three triterpenes was assessed on non-small cell lung cancer cell line; A549 using MTT assay and cell cycle analysis using annexin V/propidium iodide. The molecular mechanism underlying anti-apoptotic effects was determined by analyzing Let-7 miRNA and miRNA-21 expression, the mRNA gene expression level of Bax, CASP-8, CD95, Bcl2, KRAS, VEGF, Cyclin D1 using qRT-PCR. Our results revealed that the three isolated compounds ALUP, LUP, and BA caused cell cycle arrest at the G2/M phase with an increase in the apoptosis which may be attributed to their significant effect on raising Bax, CASP-8, and CD95 and reducing the mRNA expression levels of Bcl-2, KRAS, VEGF, and Cyclin D1 compared to control cells. RT-PCR results showed that the ALUP, LUP, and BA significantly downregulated miRNA-21 expression. Meanwhile, the three compounds caused significant overexpression of Let-7 miRNA. This is the first report on the anti-cancer activity of acetoxy-lup-5(6), 20(29)-diene (ALUP) in reducing the proliferation and differentiation of the A549 cell line through inducing apoptosis. Finally, by targeting the Let-7 miRNA/Cyclin D1/VEGF cascade, acetoxy-lup-5(6), 20(29)-diene could be a potential therapeutic agent for lung cancer. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12906-023-04201-7. BioMed Central 2023-10-16 /pmc/articles/PMC10577955/ /pubmed/37845669 http://dx.doi.org/10.1186/s12906-023-04201-7 Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/Open Access This 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
Aborehab, Nora M.
Salama, Maha M.
Ezzat, Shahira M.
A novel lupene derivative from Thymus capitatus possesses an apoptosis-inducing effect via Let-7 miRNA/Cyclin D1/VEGF cascade in the A549 cell line
title A novel lupene derivative from Thymus capitatus possesses an apoptosis-inducing effect via Let-7 miRNA/Cyclin D1/VEGF cascade in the A549 cell line
title_full A novel lupene derivative from Thymus capitatus possesses an apoptosis-inducing effect via Let-7 miRNA/Cyclin D1/VEGF cascade in the A549 cell line
title_fullStr A novel lupene derivative from Thymus capitatus possesses an apoptosis-inducing effect via Let-7 miRNA/Cyclin D1/VEGF cascade in the A549 cell line
title_full_unstemmed A novel lupene derivative from Thymus capitatus possesses an apoptosis-inducing effect via Let-7 miRNA/Cyclin D1/VEGF cascade in the A549 cell line
title_short A novel lupene derivative from Thymus capitatus possesses an apoptosis-inducing effect via Let-7 miRNA/Cyclin D1/VEGF cascade in the A549 cell line
title_sort novel lupene derivative from thymus capitatus possesses an apoptosis-inducing effect via let-7 mirna/cyclin d1/vegf cascade in the a549 cell line
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10577955/
https://www.ncbi.nlm.nih.gov/pubmed/37845669
http://dx.doi.org/10.1186/s12906-023-04201-7
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