Parthenolide (PTL) is a natural product derived from the feverfew plant (<i>Tanacetum parthenium</i>), demonstrated to selectively induce apoptosis in leukemia stem cells over non-cancerous hemotopoietic stem cells. Cancer stem cells (CSCs) are resistant to a number of common therapies, and therefore, are drivers of disease relapse and metastasis. Elucidating the targets and mechanisms that confers the selective cytotoxicity of PTL will aid in the development of more effective therapies. Various studies have determined that parthenolide can inhibit NF-kB signaling; however, knockdown of NF-κB signaling in primary acute myeloid leukemia (AML) cells does not completely kill AML CSCs. Therefore, this project aims to use cellular pulldown and proteomic methods to identify molecular targets of parthenolide in both glioblastoma and AML cells. Alkyne analogues of PTL were synthesized and dosed to both glioblastoma and AML cells, and the covalent targets of the compound was identified by LC-MS/MS analysis of the isolated peptides. The protein targets were further corroborated by companion genomic studies using RNA-sequencing studies. These results and ongoing studies will be presented.

Parthenolide-alkyne pulldown studies to identify molecular targets in glioblastoma and acute myeloid leukemia cells

2019 Fall National Meeting

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