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Preclinical Evaluation of Artesunate as an Antineoplastic Agent in Ovarian Cancer Treatment

Background: Ovarian cancer is the deadliest gynecologic malignancy despite current first-line treatment with a platinum and taxane doublet. Artesunate has broad antineoplastic properties but has not been investigated in combination with carboplatin and paclitaxel for ovarian cancer treatment. Method...

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Autores principales: McDowell, Anthony, Hill, Kristen S., McCorkle, Joseph Robert, Gorski, Justin, Zhang, Yilin, Salahudeen, Ameen A., Ueland, Fred, Kolesar, Jill M.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7996621/
https://www.ncbi.nlm.nih.gov/pubmed/33652561
http://dx.doi.org/10.3390/diagnostics11030395
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author McDowell, Anthony
Hill, Kristen S.
McCorkle, Joseph Robert
Gorski, Justin
Zhang, Yilin
Salahudeen, Ameen A.
Ueland, Fred
Kolesar, Jill M.
author_facet McDowell, Anthony
Hill, Kristen S.
McCorkle, Joseph Robert
Gorski, Justin
Zhang, Yilin
Salahudeen, Ameen A.
Ueland, Fred
Kolesar, Jill M.
author_sort McDowell, Anthony
collection PubMed
description Background: Ovarian cancer is the deadliest gynecologic malignancy despite current first-line treatment with a platinum and taxane doublet. Artesunate has broad antineoplastic properties but has not been investigated in combination with carboplatin and paclitaxel for ovarian cancer treatment. Methods: Standard cell culture technique with commercially available ovarian cancer cell lines were utilized in cell viability, DNA damage, and cell cycle progression assays to qualify and quantify artesunate treatment effects. Additionally, the sequence of administering artesunate in combination with paclitaxel and carboplatin was determined. The activity of artesunate was also assessed in 3D organoid models of primary ovarian cancer and RNAseq analysis was utilized to identify genes and the associated genetic pathways that were differentially regulated in artesunate resistant organoid models compared to organoids that were sensitive to artesunate. Results: Artesunate treatment reduces cell viability in 2D and 3D ovarian cancer cell models. Clinically relevant concentrations of artesunate induce G1 arrest, but do not induce DNA damage. Pathways related to cell cycle progression, specifically G1/S transition, are upregulated in ovarian organoid models that are innately more resistant to artesunate compared to more sensitive models. Depending on the sequence of administration, the addition of artesunate to carboplatin and paclitaxel improves their effectiveness. Conclusions: Artesunate has preclinical activity in ovarian cancer that merits further investigation to treat ovarian cancer.
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spelling pubmed-79966212021-03-27 Preclinical Evaluation of Artesunate as an Antineoplastic Agent in Ovarian Cancer Treatment McDowell, Anthony Hill, Kristen S. McCorkle, Joseph Robert Gorski, Justin Zhang, Yilin Salahudeen, Ameen A. Ueland, Fred Kolesar, Jill M. Diagnostics (Basel) Article Background: Ovarian cancer is the deadliest gynecologic malignancy despite current first-line treatment with a platinum and taxane doublet. Artesunate has broad antineoplastic properties but has not been investigated in combination with carboplatin and paclitaxel for ovarian cancer treatment. Methods: Standard cell culture technique with commercially available ovarian cancer cell lines were utilized in cell viability, DNA damage, and cell cycle progression assays to qualify and quantify artesunate treatment effects. Additionally, the sequence of administering artesunate in combination with paclitaxel and carboplatin was determined. The activity of artesunate was also assessed in 3D organoid models of primary ovarian cancer and RNAseq analysis was utilized to identify genes and the associated genetic pathways that were differentially regulated in artesunate resistant organoid models compared to organoids that were sensitive to artesunate. Results: Artesunate treatment reduces cell viability in 2D and 3D ovarian cancer cell models. Clinically relevant concentrations of artesunate induce G1 arrest, but do not induce DNA damage. Pathways related to cell cycle progression, specifically G1/S transition, are upregulated in ovarian organoid models that are innately more resistant to artesunate compared to more sensitive models. Depending on the sequence of administration, the addition of artesunate to carboplatin and paclitaxel improves their effectiveness. Conclusions: Artesunate has preclinical activity in ovarian cancer that merits further investigation to treat ovarian cancer. MDPI 2021-02-26 /pmc/articles/PMC7996621/ /pubmed/33652561 http://dx.doi.org/10.3390/diagnostics11030395 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 (http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) ).
spellingShingle Article
McDowell, Anthony
Hill, Kristen S.
McCorkle, Joseph Robert
Gorski, Justin
Zhang, Yilin
Salahudeen, Ameen A.
Ueland, Fred
Kolesar, Jill M.
Preclinical Evaluation of Artesunate as an Antineoplastic Agent in Ovarian Cancer Treatment
title Preclinical Evaluation of Artesunate as an Antineoplastic Agent in Ovarian Cancer Treatment
title_full Preclinical Evaluation of Artesunate as an Antineoplastic Agent in Ovarian Cancer Treatment
title_fullStr Preclinical Evaluation of Artesunate as an Antineoplastic Agent in Ovarian Cancer Treatment
title_full_unstemmed Preclinical Evaluation of Artesunate as an Antineoplastic Agent in Ovarian Cancer Treatment
title_short Preclinical Evaluation of Artesunate as an Antineoplastic Agent in Ovarian Cancer Treatment
title_sort preclinical evaluation of artesunate as an antineoplastic agent in ovarian cancer treatment
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7996621/
https://www.ncbi.nlm.nih.gov/pubmed/33652561
http://dx.doi.org/10.3390/diagnostics11030395
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