A novel anti-mitotic activity on human cells by Pulchelloid A, a compound isolated from the prairie plant Gaillardia aristata

Abstract

In this thesis we investigate the prairie plant species Gaillardia aristata for compounds of biological interest. Through the use of phenotypic screens based upon the hallmarks of cancer, we have characterized the effects of G. aristata extracts upon human cell lines, and found that extracts induced mitotic arrest. This arrest was characterized by low levels of pTyr15-Cdk1, and high levels of cyclin B, securin, and pThr320-PP1Cα, indicating that cells arrested at metaphase-anaphase transition. Arrested cells exhibited distorted mitotic spindles and damaged DNA. By biology-guided fractionation, we isolated a compound from G. aristata plant extracts that inhibits mitosis in human cells. The compound was the sesquiterpene lactone Pulchelloid A, and we are the first to identify its activities upon human cells. Pulchelloid A affects mitosis through a mechanism that could involve the inhibition of the ubiquitin-proteasome pathway. Insight into this mitotic process might be beneficial to future studies in cancer therapies.