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Withania somnifera Modulates Radiation-Induced Generation of Lung Cancer Stem Cells via Restraining the Hedgehog Signaling Factors

Cancer stem cells (CSCs) are implicated in the genesis, development, and recurrence of lung cancer (LC) with great resistance to radiation and chemotherapy. The aim of this study is to assess the inhibitory potential of ethanol extract of Withania somnifera (WS); 500 mg/kg body-weight/day and 8 Gy o...

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Autores principales: Moustafa, Enas Mahmoud, Abdel Salam, Hemat Sameeh, Mansour, Somaya Zakaria
Formato: Online Artículo Texto
Lenguaje:English
Publicado: SAGE Publications 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8891860/
https://www.ncbi.nlm.nih.gov/pubmed/35250409
http://dx.doi.org/10.1177/15593258221076711
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author Moustafa, Enas Mahmoud
Abdel Salam, Hemat Sameeh
Mansour, Somaya Zakaria
author_facet Moustafa, Enas Mahmoud
Abdel Salam, Hemat Sameeh
Mansour, Somaya Zakaria
author_sort Moustafa, Enas Mahmoud
collection PubMed
description Cancer stem cells (CSCs) are implicated in the genesis, development, and recurrence of lung cancer (LC) with great resistance to radiation and chemotherapy. The aim of this study is to assess the inhibitory potential of ethanol extract of Withania somnifera (WS); 500 mg/kg body-weight/day and 8 Gy of ionizing radiation (IR) could inhibit the stemness gene and confer the radiosensitizing effect of W. somnifera extract in the female rat LC model. Compared to IR or WS, the in vitro assay showed that WS + IR potentiates proliferation-inhibition and cell death of the A-549 cell line and suppresses sphere formation. The Hedgehog (Hh) signaling associated with the expression levels of lung CSC markers, octamer-binding transcription factor-4 (OCT4), SRY-box 2 (SOX2), CD133, ATP Binding Cassette Subfamily G Member 2 (ABCG2), and NANOG was upregulated with stimulated epithelial-to-mesenchymal transition (EMT) indicators α-smooth muscle actin (α-SMA), Drosophila embryonic protein (SNAIL-1), Vimentin, and E-cadherin in the LC rat model. The W. somnifera extract plus IR inhibits Hh activation factors, which has resulted in the suppression of CSC gene markers and EMT factors. W. somnifera extract may be a significant adjuvant in the course of radiotherapy, contributing to the termination of tumor progression, and thus providing cure insights into the molecular mechanisms of lung CSCs intervention.
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spelling pubmed-88918602022-03-04 Withania somnifera Modulates Radiation-Induced Generation of Lung Cancer Stem Cells via Restraining the Hedgehog Signaling Factors Moustafa, Enas Mahmoud Abdel Salam, Hemat Sameeh Mansour, Somaya Zakaria Dose Response Original Article Cancer stem cells (CSCs) are implicated in the genesis, development, and recurrence of lung cancer (LC) with great resistance to radiation and chemotherapy. The aim of this study is to assess the inhibitory potential of ethanol extract of Withania somnifera (WS); 500 mg/kg body-weight/day and 8 Gy of ionizing radiation (IR) could inhibit the stemness gene and confer the radiosensitizing effect of W. somnifera extract in the female rat LC model. Compared to IR or WS, the in vitro assay showed that WS + IR potentiates proliferation-inhibition and cell death of the A-549 cell line and suppresses sphere formation. The Hedgehog (Hh) signaling associated with the expression levels of lung CSC markers, octamer-binding transcription factor-4 (OCT4), SRY-box 2 (SOX2), CD133, ATP Binding Cassette Subfamily G Member 2 (ABCG2), and NANOG was upregulated with stimulated epithelial-to-mesenchymal transition (EMT) indicators α-smooth muscle actin (α-SMA), Drosophila embryonic protein (SNAIL-1), Vimentin, and E-cadherin in the LC rat model. The W. somnifera extract plus IR inhibits Hh activation factors, which has resulted in the suppression of CSC gene markers and EMT factors. W. somnifera extract may be a significant adjuvant in the course of radiotherapy, contributing to the termination of tumor progression, and thus providing cure insights into the molecular mechanisms of lung CSCs intervention. SAGE Publications 2022-02-24 /pmc/articles/PMC8891860/ /pubmed/35250409 http://dx.doi.org/10.1177/15593258221076711 Text en © The Author(s) 2022 https://creativecommons.org/licenses/by-nc/4.0/This article is distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 License (https://creativecommons.org/licenses/by-nc/4.0/) which permits non-commercial use, reproduction and distribution of the work without further permission provided the original work is attributed as specified on the SAGE and Open Access pages (https://us.sagepub.com/en-us/nam/open-access-at-sage).
spellingShingle Original Article
Moustafa, Enas Mahmoud
Abdel Salam, Hemat Sameeh
Mansour, Somaya Zakaria
Withania somnifera Modulates Radiation-Induced Generation of Lung Cancer Stem Cells via Restraining the Hedgehog Signaling Factors
title Withania somnifera Modulates Radiation-Induced Generation of Lung Cancer Stem Cells via Restraining the Hedgehog Signaling Factors
title_full Withania somnifera Modulates Radiation-Induced Generation of Lung Cancer Stem Cells via Restraining the Hedgehog Signaling Factors
title_fullStr Withania somnifera Modulates Radiation-Induced Generation of Lung Cancer Stem Cells via Restraining the Hedgehog Signaling Factors
title_full_unstemmed Withania somnifera Modulates Radiation-Induced Generation of Lung Cancer Stem Cells via Restraining the Hedgehog Signaling Factors
title_short Withania somnifera Modulates Radiation-Induced Generation of Lung Cancer Stem Cells via Restraining the Hedgehog Signaling Factors
title_sort withania somnifera modulates radiation-induced generation of lung cancer stem cells via restraining the hedgehog signaling factors
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8891860/
https://www.ncbi.nlm.nih.gov/pubmed/35250409
http://dx.doi.org/10.1177/15593258221076711
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