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Dinactin: A New Antitumor Antibiotic with Cell Cycle Progression and Cancer Stemness Inhibiting Activities in Lung Cancer

Lung cancer, especially non-small cell lung cancer (NSCLC), is one of the most complex diseases, despite the existence of effective treatments such as chemotherapy and immunotherapy. Since cancer stem cells (CSCs) are responsible for chemo- and radio-resistance, metastasis, and cancer recurrence, fi...

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Autores principales: Rawangkan, Anchalee, Wongsirisin, Pattama, Pook-In, Grissana, Siriphap, Achiraya, Yosboonruang, Atchariya, Kiddee, Anong, Chuerduangphui, Jureeporn, Reukngam, Nanthawan, Duangjai, Acharaporn, Saokaew, Surasak, Praphasawat, Ratsada
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9774622/
https://www.ncbi.nlm.nih.gov/pubmed/36551502
http://dx.doi.org/10.3390/antibiotics11121845
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author Rawangkan, Anchalee
Wongsirisin, Pattama
Pook-In, Grissana
Siriphap, Achiraya
Yosboonruang, Atchariya
Kiddee, Anong
Chuerduangphui, Jureeporn
Reukngam, Nanthawan
Duangjai, Acharaporn
Saokaew, Surasak
Praphasawat, Ratsada
author_facet Rawangkan, Anchalee
Wongsirisin, Pattama
Pook-In, Grissana
Siriphap, Achiraya
Yosboonruang, Atchariya
Kiddee, Anong
Chuerduangphui, Jureeporn
Reukngam, Nanthawan
Duangjai, Acharaporn
Saokaew, Surasak
Praphasawat, Ratsada
author_sort Rawangkan, Anchalee
collection PubMed
description Lung cancer, especially non-small cell lung cancer (NSCLC), is one of the most complex diseases, despite the existence of effective treatments such as chemotherapy and immunotherapy. Since cancer stem cells (CSCs) are responsible for chemo- and radio-resistance, metastasis, and cancer recurrence, finding new therapeutic targets for CSCs is critical. Dinactin is a natural secondary metabolite produced by microorganisms. Recently, dinactin has been revealed as a promising antitumor antibiotic via various mechanisms. However, the evidence relating to cell cycle progression regulation is constrained, and effects on cancer stemness have not been elucidated. Therefore, the aim of this study is to evaluate the new function of dinactin in anti-NSCLC proliferation, focusing on cell cycle progression and cancer stemness properties in Lu99 and A549 cells. Flow cytometry and immunoblotting analyses revealed that 0.1–1 µM of dinactin suppresses cell growth through induction of the G(0)/G(1) phase associated with down-regulation of cyclins A, B, and D3, and cdk2 protein expression. The tumor-sphere forming capacity was used to assess the effect of dinactin on the cancer stemness potential in NSCLC cells. At a concentration of 1 nM, dinactin reduced both the number and size of the tumor-spheres. The quantitative RT-PCR analyses indicated that dinactin suppressed sphere formation by significantly reducing expression of CSC markers (i.e., ALDH1A1, Nanog, Oct4, and Sox2) in Lu99 cells. Consequently, dinactin could be a promising strategy for NSCLC therapy targeting CSCs.
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spelling pubmed-97746222022-12-23 Dinactin: A New Antitumor Antibiotic with Cell Cycle Progression and Cancer Stemness Inhibiting Activities in Lung Cancer Rawangkan, Anchalee Wongsirisin, Pattama Pook-In, Grissana Siriphap, Achiraya Yosboonruang, Atchariya Kiddee, Anong Chuerduangphui, Jureeporn Reukngam, Nanthawan Duangjai, Acharaporn Saokaew, Surasak Praphasawat, Ratsada Antibiotics (Basel) Article Lung cancer, especially non-small cell lung cancer (NSCLC), is one of the most complex diseases, despite the existence of effective treatments such as chemotherapy and immunotherapy. Since cancer stem cells (CSCs) are responsible for chemo- and radio-resistance, metastasis, and cancer recurrence, finding new therapeutic targets for CSCs is critical. Dinactin is a natural secondary metabolite produced by microorganisms. Recently, dinactin has been revealed as a promising antitumor antibiotic via various mechanisms. However, the evidence relating to cell cycle progression regulation is constrained, and effects on cancer stemness have not been elucidated. Therefore, the aim of this study is to evaluate the new function of dinactin in anti-NSCLC proliferation, focusing on cell cycle progression and cancer stemness properties in Lu99 and A549 cells. Flow cytometry and immunoblotting analyses revealed that 0.1–1 µM of dinactin suppresses cell growth through induction of the G(0)/G(1) phase associated with down-regulation of cyclins A, B, and D3, and cdk2 protein expression. The tumor-sphere forming capacity was used to assess the effect of dinactin on the cancer stemness potential in NSCLC cells. At a concentration of 1 nM, dinactin reduced both the number and size of the tumor-spheres. The quantitative RT-PCR analyses indicated that dinactin suppressed sphere formation by significantly reducing expression of CSC markers (i.e., ALDH1A1, Nanog, Oct4, and Sox2) in Lu99 cells. Consequently, dinactin could be a promising strategy for NSCLC therapy targeting CSCs. MDPI 2022-12-19 /pmc/articles/PMC9774622/ /pubmed/36551502 http://dx.doi.org/10.3390/antibiotics11121845 Text en © 2022 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
Rawangkan, Anchalee
Wongsirisin, Pattama
Pook-In, Grissana
Siriphap, Achiraya
Yosboonruang, Atchariya
Kiddee, Anong
Chuerduangphui, Jureeporn
Reukngam, Nanthawan
Duangjai, Acharaporn
Saokaew, Surasak
Praphasawat, Ratsada
Dinactin: A New Antitumor Antibiotic with Cell Cycle Progression and Cancer Stemness Inhibiting Activities in Lung Cancer
title Dinactin: A New Antitumor Antibiotic with Cell Cycle Progression and Cancer Stemness Inhibiting Activities in Lung Cancer
title_full Dinactin: A New Antitumor Antibiotic with Cell Cycle Progression and Cancer Stemness Inhibiting Activities in Lung Cancer
title_fullStr Dinactin: A New Antitumor Antibiotic with Cell Cycle Progression and Cancer Stemness Inhibiting Activities in Lung Cancer
title_full_unstemmed Dinactin: A New Antitumor Antibiotic with Cell Cycle Progression and Cancer Stemness Inhibiting Activities in Lung Cancer
title_short Dinactin: A New Antitumor Antibiotic with Cell Cycle Progression and Cancer Stemness Inhibiting Activities in Lung Cancer
title_sort dinactin: a new antitumor antibiotic with cell cycle progression and cancer stemness inhibiting activities in lung cancer
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9774622/
https://www.ncbi.nlm.nih.gov/pubmed/36551502
http://dx.doi.org/10.3390/antibiotics11121845
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