Identification of inhibitors of ovarian cancer stem-like cells by high-throughput screening

Background: Ovarian cancer stem cells are characterized by self-renewal capacity, ability to differentiate into distinct lineages, as well as higher invasiveness and resistance to many anticancer agents. Since they may be responsible for the recurrence of ovarian cancer after initial response to chemotherapy, development of new therapies targeting this special cellular subpopulation embedded within bulk ovarian cancers is warranted. Methods: A high-throughput screening (HTS) campaign was performed with 825 compounds from the Mechanistic Set chemical library [Developmental Therapeutics Program (DTP)/National Cancer Institute (NCI)] against ovarian cancer stem-like cells (CSC) using a resazurin-based cell cytotoxicity assay. Identified sets of active compounds were projected onto self-organizing maps to identify their putative cellular response groups. Results: From 793 screening compounds with evaluable data, 158 were found to have significant inhibitory effects on ovarian CSC. Computational analysis indicates that the majority of these compounds are associated with mitotic cellular responses. Conclusions: Our HTS has uncovered a number of candidate compounds that may, after further testing, prove effective in targeting both ovarian CSC and their more differentiated progeny.