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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| Format: | Article |
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MDPI AG
2021-02-01
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| Series: | Diagnostics |
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| Online Access: | https://www.mdpi.com/2075-4418/11/3/395 |
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| author | Anthony McDowell Kristen S. Hill Joseph Robert McCorkle Justin Gorski Yilin Zhang Ameen A. Salahudeen Fred Ueland Jill M. Kolesar |
| author_facet | Anthony McDowell Kristen S. Hill Joseph Robert McCorkle Justin Gorski Yilin Zhang Ameen A. Salahudeen Fred Ueland Jill M. Kolesar |
| author_sort | Anthony McDowell |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-03-09T00:31:47Z |
| format | Article |
| id | doaj.art-bb8018390a4a44f78527de2fc00ee88f |
| institution | Directory Open Access Journal |
| issn | 2075-4418 |
| language | English |
| last_indexed | 2024-03-09T00:31:47Z |
| publishDate | 2021-02-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Diagnostics |
| spelling | doaj.art-bb8018390a4a44f78527de2fc00ee88f2023-12-11T18:30:05ZengMDPI AGDiagnostics2075-44182021-02-0111339510.3390/diagnostics11030395Preclinical Evaluation of Artesunate as an Antineoplastic Agent in Ovarian Cancer TreatmentAnthony McDowell0Kristen S. Hill1Joseph 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, USABackground: 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 cancerdihydroartemisininArtemesia annuacarboplatinpaclitaxel |
| spellingShingle | Anthony McDowell Kristen S. Hill Joseph 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 Artemesia annua carboplatin paclitaxel |
| 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 | artesunate ovarian cancer dihydroartemisinin Artemesia annua carboplatin paclitaxel |
| url | https://www.mdpi.com/2075-4418/11/3/395 |
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