Identification of compounds that augment the lectin-sensitivity of Chinese Hamster Ovary cells

Abstract

Glycosylation is now recognized as one of the most important modifications of eukaryotic proteins. In cancer biology, alterations in cell surface glycosylation have been exploited as valuable biomarkers, and the relationship of this modification to the metastatic characteristics of cancer cells has also been well-documented. Chemicals that can alter cell surface glycosylation patterns will therefore become attractive lead compounds for controlling the metastatic characteristics of cancer cells, one of the critical factors in their malignancy and prognosis of the disease. In this study, we established a system for screening compounds that have the potential to alter cell surface glycosylation by taking advantage of the susceptibility of cells toward various lectins. Through our screening of a chemical library, we were able to identify two compounds that augment the sensitivity of Chinese Hamster Ovary (CHO-K1) cells against the L4-PHA lectin. Surprisingly, these compounds did not result in alterations in cell surface glycan structures. Instead, they appeared to render the cells to be more sensitive to various lectins with distinct carbohydrate specificities. These compounds promise to be valuable, not only as tools for providing insights into the intracellular signaling of lectin-mediated growth arrest, but also as potential lead compounds for use as therapeutic, anti-cancer drugs.