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Silibinin Regulates Tumor Progression and Tumorsphere Formation by Suppressing PD-L1 Expression in Non-Small Cell Lung Cancer (NSCLC) Cells

Recently, natural compounds have been used globally for cancer treatment studies. Silibinin is a natural compound extracted from Silybum marianum (milk thistle), which has been suggested as an anticancer drug through various studies. Studies on its activity in various cancers are undergoing. This st...

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Autores principales: Rugamba, Alexis, Kang, Dong Young, Sp, Nipin, Jo, Eun Seong, Lee, Jin-Moo, Bae, Se Won, Jang, Kyoung-Jin
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8307196/
https://www.ncbi.nlm.nih.gov/pubmed/34209829
http://dx.doi.org/10.3390/cells10071632
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author Rugamba, Alexis
Kang, Dong Young
Sp, Nipin
Jo, Eun Seong
Lee, Jin-Moo
Bae, Se Won
Jang, Kyoung-Jin
author_facet Rugamba, Alexis
Kang, Dong Young
Sp, Nipin
Jo, Eun Seong
Lee, Jin-Moo
Bae, Se Won
Jang, Kyoung-Jin
author_sort Rugamba, Alexis
collection PubMed
description Recently, natural compounds have been used globally for cancer treatment studies. Silibinin is a natural compound extracted from Silybum marianum (milk thistle), which has been suggested as an anticancer drug through various studies. Studies on its activity in various cancers are undergoing. This study demonstrated the molecular signaling behind the anticancer activity of silibinin in non-small cell lung cancer (NSCLC). Quantitative real-time polymerase chain reaction and Western blotting analysis were performed for molecular signaling analysis. Wound healing assay, invasion assay, and in vitro angiogenesis were performed for the anticancer activity of silibinin. The results indicated that silibinin inhibited A549, H292, and H460 cell proliferation in a concentration-dependent manner, as confirmed by the induction of G0/G1 cell cycle arrest and apoptosis and the inhibition of tumor angiogenesis, migration, and invasion. This study also assessed the role of silibinin in suppressing tumorsphere formation using the tumorsphere formation assay. By binding to the epidermal growth factor receptor (EGFR), silibinin downregulated phosphorylated EGFR expression, which then inhibited its downstream targets, the JAK2/STAT5 and PI3K/AKT pathways, and thereby reduced matrix metalloproteinase, PD-L1, and vascular endothelial growth factor expression. Binding analysis demonstrated that STAT5 binds to the PD-L1 promoter region in the nucleus and silibinin inhibited the STAT5/PD-L1 complex. Altogether, silibinin could be considered as a candidate for tumor immunotherapy and cancer stem cell-targeted therapy.
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spelling pubmed-83071962021-07-25 Silibinin Regulates Tumor Progression and Tumorsphere Formation by Suppressing PD-L1 Expression in Non-Small Cell Lung Cancer (NSCLC) Cells Rugamba, Alexis Kang, Dong Young Sp, Nipin Jo, Eun Seong Lee, Jin-Moo Bae, Se Won Jang, Kyoung-Jin Cells Article Recently, natural compounds have been used globally for cancer treatment studies. Silibinin is a natural compound extracted from Silybum marianum (milk thistle), which has been suggested as an anticancer drug through various studies. Studies on its activity in various cancers are undergoing. This study demonstrated the molecular signaling behind the anticancer activity of silibinin in non-small cell lung cancer (NSCLC). Quantitative real-time polymerase chain reaction and Western blotting analysis were performed for molecular signaling analysis. Wound healing assay, invasion assay, and in vitro angiogenesis were performed for the anticancer activity of silibinin. The results indicated that silibinin inhibited A549, H292, and H460 cell proliferation in a concentration-dependent manner, as confirmed by the induction of G0/G1 cell cycle arrest and apoptosis and the inhibition of tumor angiogenesis, migration, and invasion. This study also assessed the role of silibinin in suppressing tumorsphere formation using the tumorsphere formation assay. By binding to the epidermal growth factor receptor (EGFR), silibinin downregulated phosphorylated EGFR expression, which then inhibited its downstream targets, the JAK2/STAT5 and PI3K/AKT pathways, and thereby reduced matrix metalloproteinase, PD-L1, and vascular endothelial growth factor expression. Binding analysis demonstrated that STAT5 binds to the PD-L1 promoter region in the nucleus and silibinin inhibited the STAT5/PD-L1 complex. Altogether, silibinin could be considered as a candidate for tumor immunotherapy and cancer stem cell-targeted therapy. MDPI 2021-06-29 /pmc/articles/PMC8307196/ /pubmed/34209829 http://dx.doi.org/10.3390/cells10071632 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/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 (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Rugamba, Alexis
Kang, Dong Young
Sp, Nipin
Jo, Eun Seong
Lee, Jin-Moo
Bae, Se Won
Jang, Kyoung-Jin
Silibinin Regulates Tumor Progression and Tumorsphere Formation by Suppressing PD-L1 Expression in Non-Small Cell Lung Cancer (NSCLC) Cells
title Silibinin Regulates Tumor Progression and Tumorsphere Formation by Suppressing PD-L1 Expression in Non-Small Cell Lung Cancer (NSCLC) Cells
title_full Silibinin Regulates Tumor Progression and Tumorsphere Formation by Suppressing PD-L1 Expression in Non-Small Cell Lung Cancer (NSCLC) Cells
title_fullStr Silibinin Regulates Tumor Progression and Tumorsphere Formation by Suppressing PD-L1 Expression in Non-Small Cell Lung Cancer (NSCLC) Cells
title_full_unstemmed Silibinin Regulates Tumor Progression and Tumorsphere Formation by Suppressing PD-L1 Expression in Non-Small Cell Lung Cancer (NSCLC) Cells
title_short Silibinin Regulates Tumor Progression and Tumorsphere Formation by Suppressing PD-L1 Expression in Non-Small Cell Lung Cancer (NSCLC) Cells
title_sort silibinin regulates tumor progression and tumorsphere formation by suppressing pd-l1 expression in non-small cell lung cancer (nsclc) cells
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8307196/
https://www.ncbi.nlm.nih.gov/pubmed/34209829
http://dx.doi.org/10.3390/cells10071632
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