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Sanguinarine Induces Apoptosis in Papillary Thyroid Cancer Cells via Generation of Reactive Oxygen Species
Sanguinarine (SNG), a natural compound with an array of pharmacological activities, has promising therapeutic potential against a number of pathological conditions, including malignancies. In the present study, we have investigated the antiproliferative potential of SNG against two well-characterize...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7179475/ https://www.ncbi.nlm.nih.gov/pubmed/32182833 http://dx.doi.org/10.3390/molecules25051229 |
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author | Khan, Abdul Q. Mohamed, Elham A. N. Hakeem, Ishrat Nazeer, Aneeza Kuttikrishnan, Shilpa Prabhu, Kirti S. Siveen, Kodappully S. Nawaz, Zafar Ahmad, Aamir Zayed, Hatem Uddin, Shahab |
author_facet | Khan, Abdul Q. Mohamed, Elham A. N. Hakeem, Ishrat Nazeer, Aneeza Kuttikrishnan, Shilpa Prabhu, Kirti S. Siveen, Kodappully S. Nawaz, Zafar Ahmad, Aamir Zayed, Hatem Uddin, Shahab |
author_sort | Khan, Abdul Q. |
collection | PubMed |
description | Sanguinarine (SNG), a natural compound with an array of pharmacological activities, has promising therapeutic potential against a number of pathological conditions, including malignancies. In the present study, we have investigated the antiproliferative potential of SNG against two well-characterized papillary thyroid cancer (PTC) cell lines, BCPAP and TPC-1. SNG significantly inhibited cell proliferation of PTC cells in a dose and time-dependent manner. Western blot analysis revealed that SNG markedly attenuated deregulated expression of p-STAT3, without affecting total STAT3, and inhibited growth of PTC via activation of apoptotic and autophagy signaling cascade, as SNG treatment of PTC cells led to the activation of caspase-3 and caspase-8; cleavage of PARP and activation of autophagy markers. Further, SNG-mediated anticancer effects in PTC cells involved the generation of reactive oxygen species (ROS) as N-acetyl cysteine (NAC), an inhibitor of ROS, prevented SNG-mediated antiproliferative, apoptosis and autophagy inducing action. Interestingly, SNG also sensitized PTC cells to chemotherapeutic drug cisplatin, which was inhibited by NAC. Finally, SNG suppressed the growth of PTC thyrospheres and downregulated stemness markers ALDH2 and SOX2. Altogether, the findings of the current study suggest that SNG has anticancer potential against PTC cells as well its derived cancer stem-like cells, most likely via inactivation of STAT3 and its associated signaling molecules. |
format | Online Article Text |
id | pubmed-7179475 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-71794752020-05-05 Sanguinarine Induces Apoptosis in Papillary Thyroid Cancer Cells via Generation of Reactive Oxygen Species Khan, Abdul Q. Mohamed, Elham A. N. Hakeem, Ishrat Nazeer, Aneeza Kuttikrishnan, Shilpa Prabhu, Kirti S. Siveen, Kodappully S. Nawaz, Zafar Ahmad, Aamir Zayed, Hatem Uddin, Shahab Molecules Article Sanguinarine (SNG), a natural compound with an array of pharmacological activities, has promising therapeutic potential against a number of pathological conditions, including malignancies. In the present study, we have investigated the antiproliferative potential of SNG against two well-characterized papillary thyroid cancer (PTC) cell lines, BCPAP and TPC-1. SNG significantly inhibited cell proliferation of PTC cells in a dose and time-dependent manner. Western blot analysis revealed that SNG markedly attenuated deregulated expression of p-STAT3, without affecting total STAT3, and inhibited growth of PTC via activation of apoptotic and autophagy signaling cascade, as SNG treatment of PTC cells led to the activation of caspase-3 and caspase-8; cleavage of PARP and activation of autophagy markers. Further, SNG-mediated anticancer effects in PTC cells involved the generation of reactive oxygen species (ROS) as N-acetyl cysteine (NAC), an inhibitor of ROS, prevented SNG-mediated antiproliferative, apoptosis and autophagy inducing action. Interestingly, SNG also sensitized PTC cells to chemotherapeutic drug cisplatin, which was inhibited by NAC. Finally, SNG suppressed the growth of PTC thyrospheres and downregulated stemness markers ALDH2 and SOX2. Altogether, the findings of the current study suggest that SNG has anticancer potential against PTC cells as well its derived cancer stem-like cells, most likely via inactivation of STAT3 and its associated signaling molecules. MDPI 2020-03-09 /pmc/articles/PMC7179475/ /pubmed/32182833 http://dx.doi.org/10.3390/molecules25051229 Text en © 2020 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 Khan, Abdul Q. Mohamed, Elham A. N. Hakeem, Ishrat Nazeer, Aneeza Kuttikrishnan, Shilpa Prabhu, Kirti S. Siveen, Kodappully S. Nawaz, Zafar Ahmad, Aamir Zayed, Hatem Uddin, Shahab Sanguinarine Induces Apoptosis in Papillary Thyroid Cancer Cells via Generation of Reactive Oxygen Species |
title | Sanguinarine Induces Apoptosis in Papillary Thyroid Cancer Cells via Generation of Reactive Oxygen Species |
title_full | Sanguinarine Induces Apoptosis in Papillary Thyroid Cancer Cells via Generation of Reactive Oxygen Species |
title_fullStr | Sanguinarine Induces Apoptosis in Papillary Thyroid Cancer Cells via Generation of Reactive Oxygen Species |
title_full_unstemmed | Sanguinarine Induces Apoptosis in Papillary Thyroid Cancer Cells via Generation of Reactive Oxygen Species |
title_short | Sanguinarine Induces Apoptosis in Papillary Thyroid Cancer Cells via Generation of Reactive Oxygen Species |
title_sort | sanguinarine induces apoptosis in papillary thyroid cancer cells via generation of reactive oxygen species |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7179475/ https://www.ncbi.nlm.nih.gov/pubmed/32182833 http://dx.doi.org/10.3390/molecules25051229 |
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