Journal article
Preclinical Evaluation of Artesunate as an Antineoplastic Agent in Ovarian Cancer Treatment
Diagnostics (Basel), Vol.11(3), 395
02/26/2021
DOI: 10.3390/diagnostics11030395
PMCID: PMC7996621
PMID: 33652561
Abstract
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.
Details
- Title: Subtitle
- Preclinical Evaluation of Artesunate as an Antineoplastic Agent in Ovarian Cancer Treatment
- Creators
- Anthony McDowell - University of KentuckyKristen S. Hill - Markey Cancer CenterJoseph Robert McCorkle - Markey Cancer CenterJustin Gorski - University of KentuckyYilin Zhang - Tempus LabsAmeen A. Salahudeen - Tempus LabsFred Ueland - University of KentuckyJill M. Kolesar - University of Kentucky
- Resource Type
- Journal article
- Publication Details
- Diagnostics (Basel), Vol.11(3), 395
- Publisher
- Mdpi
- DOI
- 10.3390/diagnostics11030395
- PMID
- 33652561
- PMCID
- PMC7996621
- ISSN
- 2075-4418
- eISSN
- 2075-4418
- Number of pages
- 15
- Grant note
- T32 CA160003 / National Cancer Institute; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Cancer Institute (NCI) P30 CA177558 / NCI Center Core Support Grant
- Language
- English
- Date published
- 02/26/2021
- Academic Unit
- Pharmacy; Pharmaceutical Sciences and Experimental Therapeutics
- Record Identifier
- 9984696540502771
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