Yeast strains heterozygous for YTA12 are sensitive to the anti‐cancer compound Parthenolide

Abstract

Parthenolide (PTL) is a naturally occurring small molecule that is the active ingredient in herbal medications used as a remedy for inflammation and pain. PTL exhibits exceptional anti‐cancer and anti‐inflammatory properties, making it a prominent candidate for furtherstudies and drug development. Acute myeloid Leukemia (AML) is a cancer of the blood, characterized by an overproduction of abnormal white blood cells that accumulate in the bone marrow. When acute myeloid leukemia cells are treated with PTL, there is a significant decrease in the function of the AML cells without altering or effecting normal cells. This is in contrast to current treatment for AML that are toxic and harmful to not only the cancer cells, but normal cells in the body. In hopes of better understanding the mechanism of PTL, the Haploinsufficiency Profiling (HIP) Assay was performedon Saccharomyces cerevisiae (bakers yeast). The HIP Assay consists of a complete set of heterozygous deletion strains that are grown in the presence of a compound of interest, strains most sensitive to the compound often carry deletions in genes that encode the drug target. The HIP Assay was performed in the presence of PTL. Yeast lacking one copy of the YTA12 gene, showed increased sensitivity to PTL. YTA12 encodes for a protein that iscomponent of the inner membrane protease that plays an important role in the degradation of incorrectly folded proteins. The hypersensitivity of the strain to PTL has been confirmed and current work is focused on determining the effect PTL has on the levelof YTA12 mRNA and protein.