Preclinical evaluation of artesunate as an antineoplastic agent in ovarian cancer treatment

Anthony McDowell, Kristen S. Hill, Joseph Robert McCorkle, Justin Gorski, Yilin Zhang, Ameen A. Salahudeen, Fred Ueland, Jill M. Kolesar

Research output: Contribution to journalArticlepeer-review

9 Scopus citations

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.

Original languageEnglish
Article number395
JournalDiagnostics
Volume11
Issue number3
DOIs
StatePublished - Mar 2021

Bibliographical note

Funding Information:
Funding: This research was partially funded by the National Cancer Institute, grant number T32 CA160003. The Biospecimen Procurement and Translational Pathology Shared Resource Facility is sup-ported by NCI Center Core Support Grant (P30 CA177558) to the University of Kentucky Markey Cancer Center.

Funding Information:
Acknowledgments: The UK Flow Cytometry & Immune Monitoring core facility is supported in part by the Office of the Vice President for Research, the Markey Cancer Center and an NCI Center Core Support Grant (P30 CA177558) to the University of Kentucky Markey Cancer Center.

Publisher Copyright:
© 2021 by the authors. Licensee MDPI, Basel, Switzerland.

Keywords

  • Artemesia annua
  • Artesunate
  • Carboplatin
  • Dihydroartemisinin
  • Ovarian cancer
  • Paclitaxel

ASJC Scopus subject areas

  • Clinical Biochemistry

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