Speaker: Nobumoto Watanabe
Unit Leader, Bio-Active Compounds Discovery Research Unit, RIKEN Center for Sustainable Resource Science
Title: Small molecule inhibitors of cancer stem cells identified through target-based and cell based screening
Abstract: Cancer Stem Cells (CSCs) exist in tumors and are involved in therapeutic resistance and relapse of tumors. Commonly used drugs in cancer therapies efficiently kill the rapidly proliferating cancer cells. However, most of those drugs are ineffective against CSCs leading to relapse. Thus the development of safe antitumor drugs that target CSCs is an urgent need. For this, we promote two strategies to isolate small molecules that inhibit the maintenance and proliferation of cancer stem cells. One is target based screening to isolate inhibitors of enzymes expressed in CSCs. The other is phenotype or cell based screening where small molecules that specifically inhibit CSCs are directly screened using model CSC like cells. In this seminar, isolation of inhibitors of phosphorylation dependent peptidyl prolyl isomeras Pin1 as an example of target-based screening will be presented. As an example of cell based screening, identification of artesunate, an antimalarial drug, as a selective inhibitor of cancer stemness will be shown. Artesunate induced mitochondrial dysfunction that selectively inhibited cancer stemness of iCSCL cells.