Preclinical Evaluation of Artesunate as an Antineoplastic Agent in Ovarian Cancer Treatment
<b> </b>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 canc...
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doaj-bb8018390a4a44f78527de2fc00ee88f2021-02-27T00:00:16ZengMDPI AGDiagnostics2075-44182021-02-011139539510.3390/diagnostics11030395Preclinical Evaluation of Artesunate as an Antineoplastic Agent in Ovarian Cancer TreatmentAnthony McDowell0Kristen S. Hill1J. Robert McCorkle2Justin Gorski3Yilin Zhang4Ameen A. Salahudeen5Fred Ueland6Jill M. Kolesar7Department of Obstetrics and Gynecology, Division of Gynecologic Oncology, College of Medicine, University of Kentucky, Lexington, KY 40536, USAMarkey Cancer Center, University of Kentucky, Lexington, KY 40536, USAMarkey Cancer Center, University of Kentucky, Lexington, KY 40536, USADepartment of Obstetrics and Gynecology, Division of Gynecologic Oncology, College of Medicine, University of Kentucky, Lexington, KY 40536, USATempus Labs, 600 W Chicago Ave. Ste 510, Chicago, IL 60654, USATempus Labs, 600 W Chicago Ave. Ste 510, Chicago, IL 60654, USADepartment of Obstetrics and Gynecology, Division of Gynecologic Oncology, College of Medicine, University of Kentucky, Lexington, KY 40536, USAMarkey Cancer Center, University of Kentucky, Lexington, KY 40536, USA<b> </b>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.https://www.mdpi.com/2075-4418/11/3/395artesunateovarian cancerdihydroartemisinin<i>Artemesia annua</i>carboplatinpaclitaxel |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Anthony McDowell Kristen S. Hill J. Robert McCorkle Justin Gorski Yilin Zhang Ameen A. Salahudeen Fred Ueland Jill M. Kolesar |
spellingShingle |
Anthony McDowell Kristen S. Hill J. Robert McCorkle Justin Gorski Yilin Zhang Ameen A. Salahudeen Fred Ueland Jill M. Kolesar Preclinical Evaluation of Artesunate as an Antineoplastic Agent in Ovarian Cancer Treatment Diagnostics artesunate ovarian cancer dihydroartemisinin <i>Artemesia annua</i> carboplatin paclitaxel |
author_facet |
Anthony McDowell Kristen S. Hill J. Robert McCorkle Justin Gorski Yilin Zhang Ameen A. Salahudeen Fred Ueland Jill M. Kolesar |
author_sort |
Anthony McDowell |
title |
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_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_sort |
preclinical evaluation of artesunate as an antineoplastic agent in ovarian cancer treatment |
publisher |
MDPI AG |
series |
Diagnostics |
issn |
2075-4418 |
publishDate |
2021-02-01 |
description |
<b> </b>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. |
topic |
artesunate ovarian cancer dihydroartemisinin <i>Artemesia annua</i> carboplatin paclitaxel |
url |
https://www.mdpi.com/2075-4418/11/3/395 |
work_keys_str_mv |
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