Abstract
The purpose of this research is to explore the therapeutic potential of parthenolide (PTL) to treat various hematopoietic neoplasms in dogs; additionally, some dog breeds are enriched for development of mast cell neoplasia and histiocytic sarcoma, providing translational study populations for rare and deadly human diseases. Growth inhibition assays were performed using a panel of canine mast cell, histiocytic sarcoma, lymphoma, and leukemia cell lines, with PTL alone or in combination with redox-perturbing standard-of-care therapeutics. Cell death was assessed using flow cytometry. Immunofluorescence and immunoblotting were used to assess NFκB localization and phosphorylation, respectively. All immortalized canine cell lines evaluated are sensitive to PTL therapy and undergo dose-dependent apoptosis following exposure to drug. PTL exposure leads to inhibition of NFκB, as evidenced by immunofluorescent nuclear exclusion and decreased p65 phosphorylation. Preliminary studies indicate that some standard-of-care therapeutics synergize with PTL. These initial studies show that PTL is a promising therapeutic for hematopoietic neoplasms in dogs. Murine modeling and investigation of redox perturbance are underway and will further investigate PTL’s potential in the clinical setting.
Citation Format: Lisa J. Schlein, Barbara Rose, Aubree Peterson, Douglas Thamm. Investigating the therapeutic potential of parthenolide for hematopoietic neoplasms in dogs [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 3700.
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