Pongol Methyl Ether Inhibits Akt and Suppresses Cancer Stem Cell Phenotypes in Lung Cancer Cells

Cancer stem cells (CSCs) are an important therapeutic target. The therapeutic agents targeting CSCs should lead to improved clinical outcomes. Here we have demonstrated the CSC-suppressing activity of pongol methyl ether (PME), a pure compound from <i>Millettia erythrocalyx</i>. Methods:...

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Autores principales:	Arnon Silapech, Satapat Racha, Nithikoon Aksorn, Pennapa Lafauy, Sucharat Tungsukruthai, Chanida Vinayanuwattikun, Boonchoo Sritularak, Pithi Chanvorachote
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	pongol methyl ether cancer stem cell lung cancer Akt CSC-targeting Medicine R Pharmacy and materia medica RS1-441
Acceso en línea:	https://doaj.org/article/520888d5add6491db8b0e70d547c7c33
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spelling	oai:doaj.org-article:520888d5add6491db8b0e70d547c7c332021-11-25T18:39:13ZPongol Methyl Ether Inhibits Akt and Suppresses Cancer Stem Cell Phenotypes in Lung Cancer Cells10.3390/ph141110851424-8247https://doaj.org/article/520888d5add6491db8b0e70d547c7c332021-10-01T00:00:00Zhttps://www.mdpi.com/1424-8247/14/11/1085https://doaj.org/toc/1424-8247Cancer stem cells (CSCs) are an important therapeutic target. The therapeutic agents targeting CSCs should lead to improved clinical outcomes. Here we have demonstrated the CSC-suppressing activity of pongol methyl ether (PME), a pure compound from <i>Millettia erythrocalyx</i>. Methods: CSC-suppressing effects were evaluated by spheroid formation assay and detection of CSC markers. The related CSC cell signals were evaluated by Western blot, immunofluorescence and molecular docking analysis. Proteins affected by PME treatment were subjected to bioinformatic analysis. Protein–protein interaction (PPI) networks were constructed by the Search Tool for Interactions of Chemicals (STITCH). The Kyoto Encyclopedia of Genes and Genomes (KEGG) mapper were used to confirm the underlying pathways. Results: PME (5–25 µM) significantly suppressed the ability of lung cancer cells to form colonies, grow in an anchorage-independent manner and generate tumour spheroids. PME at 25 µM significantly decreased the CSC markers (CD133 and ALDH1A1) and pluripotent transcription factors (Oct4 and Nanog). Akt, the key upstream signal of CSC control, was significantly decreased by the PME treatment. The molecular docking indicated that PME was bound to Akt-1 with a binding affinity of −9.2 kcal/mol greater than the Akt-1 inhibitor (reference compound; CQW). The STITCH network identified a total of 15 proteins interacted in PPI networks, and Akt-1 was identified as a central protein. The KEGG mapper indicated that the selected CSC markers were mostly involved in the ‘signalling pathways regulating pluripotency of stem cells’ pathway map and Akt, Oct4 and Nanog were the regulatory proteins in the dominant pathway. In addition, PME (10–25 µM) can suppress spheroid formation and reduce CSC-specific marker expression in patient-derived primary lung cancer cells. Conclusions: Our study revealed a novel pharmacological effect and the underlying mechanism of PME that can attenuate CSC phenotypes in lung cancer cells and may be developed for lung cancer therapy.Arnon SilapechSatapat RachaNithikoon AksornPennapa LafauySucharat TungsukruthaiChanida VinayanuwattikunBoonchoo SritularakPithi ChanvorachoteMDPI AGarticlepongol methyl ethercancer stem celllung cancerAktCSC-targetingMedicineRPharmacy and materia medicaRS1-441ENPharmaceuticals, Vol 14, Iss 1085, p 1085 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	pongol methyl ether cancer stem cell lung cancer Akt CSC-targeting Medicine R Pharmacy and materia medica RS1-441
spellingShingle	pongol methyl ether cancer stem cell lung cancer Akt CSC-targeting Medicine R Pharmacy and materia medica RS1-441 Arnon Silapech Satapat Racha Nithikoon Aksorn Pennapa Lafauy Sucharat Tungsukruthai Chanida Vinayanuwattikun Boonchoo Sritularak Pithi Chanvorachote Pongol Methyl Ether Inhibits Akt and Suppresses Cancer Stem Cell Phenotypes in Lung Cancer Cells
description	Cancer stem cells (CSCs) are an important therapeutic target. The therapeutic agents targeting CSCs should lead to improved clinical outcomes. Here we have demonstrated the CSC-suppressing activity of pongol methyl ether (PME), a pure compound from <i>Millettia erythrocalyx</i>. Methods: CSC-suppressing effects were evaluated by spheroid formation assay and detection of CSC markers. The related CSC cell signals were evaluated by Western blot, immunofluorescence and molecular docking analysis. Proteins affected by PME treatment were subjected to bioinformatic analysis. Protein–protein interaction (PPI) networks were constructed by the Search Tool for Interactions of Chemicals (STITCH). The Kyoto Encyclopedia of Genes and Genomes (KEGG) mapper were used to confirm the underlying pathways. Results: PME (5–25 µM) significantly suppressed the ability of lung cancer cells to form colonies, grow in an anchorage-independent manner and generate tumour spheroids. PME at 25 µM significantly decreased the CSC markers (CD133 and ALDH1A1) and pluripotent transcription factors (Oct4 and Nanog). Akt, the key upstream signal of CSC control, was significantly decreased by the PME treatment. The molecular docking indicated that PME was bound to Akt-1 with a binding affinity of −9.2 kcal/mol greater than the Akt-1 inhibitor (reference compound; CQW). The STITCH network identified a total of 15 proteins interacted in PPI networks, and Akt-1 was identified as a central protein. The KEGG mapper indicated that the selected CSC markers were mostly involved in the ‘signalling pathways regulating pluripotency of stem cells’ pathway map and Akt, Oct4 and Nanog were the regulatory proteins in the dominant pathway. In addition, PME (10–25 µM) can suppress spheroid formation and reduce CSC-specific marker expression in patient-derived primary lung cancer cells. Conclusions: Our study revealed a novel pharmacological effect and the underlying mechanism of PME that can attenuate CSC phenotypes in lung cancer cells and may be developed for lung cancer therapy.
format	article
author	Arnon Silapech Satapat Racha Nithikoon Aksorn Pennapa Lafauy Sucharat Tungsukruthai Chanida Vinayanuwattikun Boonchoo Sritularak Pithi Chanvorachote
author_facet	Arnon Silapech Satapat Racha Nithikoon Aksorn Pennapa Lafauy Sucharat Tungsukruthai Chanida Vinayanuwattikun Boonchoo Sritularak Pithi Chanvorachote
author_sort	Arnon Silapech
title	Pongol Methyl Ether Inhibits Akt and Suppresses Cancer Stem Cell Phenotypes in Lung Cancer Cells
title_short	Pongol Methyl Ether Inhibits Akt and Suppresses Cancer Stem Cell Phenotypes in Lung Cancer Cells
title_full	Pongol Methyl Ether Inhibits Akt and Suppresses Cancer Stem Cell Phenotypes in Lung Cancer Cells
title_fullStr	Pongol Methyl Ether Inhibits Akt and Suppresses Cancer Stem Cell Phenotypes in Lung Cancer Cells
title_full_unstemmed	Pongol Methyl Ether Inhibits Akt and Suppresses Cancer Stem Cell Phenotypes in Lung Cancer Cells
title_sort	pongol methyl ether inhibits akt and suppresses cancer stem cell phenotypes in lung cancer cells
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/520888d5add6491db8b0e70d547c7c33
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Pongol Methyl Ether Inhibits Akt and Suppresses Cancer Stem Cell Phenotypes in Lung Cancer Cells

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