journal contribution
posted on 2023-04-03, 13:40 authored by Yi-Te Yo, Ya-Wen Lin, Yu-Chi Wang, Curt Balch, Rui-Lan Huang, Michael W.Y. Chan, Huey-Kang Sytwu, Chi-Kuan Chen, Cheng-Chang Chang, Kenneth P. Nephew, Tim Huang, Mu-Hsien Yu, Hung-Cheng Lai <p>PDF file, 27KB, Differential stem cell signaling between CP70 and CP70sps were compared using an RT-PCR pathway-focused arrays (Stem signaling/Wnt signaling). Red indicates gene upregulation while green indicates gene downregulation, in CP70sps cells. Numbers indicate fold changes. Table S1A is a general focus array containing genes in Wnt, Notch, Hedgehog signaling pathways. Table S1B is a focus array on Wnt signaling.</p>
History
ARTICLE ABSTRACT
A recent hypothesis for cancer chemoresistance posits that cytotoxic survival of a subpopulation of tumor progenitors drives the propagation of recurrent disease, underscoring the need for new therapeutics that target such primitive cells. To discover such novel compounds active against drug-resistant ovarian cancer, we identified a subset of chemoresistant ovarian tumor cells fulfilling current definitions of cancer-initiating cells from cell lines and patient tumors using multiple stemness phenotypes, including the expression of stem cell markers, membrane dye efflux, sphere formation, potent tumorigenicity, and serial tumor propagation. We then subjected such stem-like ovarian tumor-initiating cells (OTIC) to high-throughput drug screening using more than 1,200 clinically approved drugs. Of 61 potential compounds preliminarily identified, more stringent assessments showed that the antihelmintic niclosamide selectively targets OTICs in vitro and in vivo. Gene expression arrays following OTIC treatment revealed niclosamide to disrupt multiple metabolic pathways affecting biogenetics, biogenesis, and redox regulation. These studies support niclosamide as a promising therapy for ovarian cancer and warrant further preclinical and clinical evaluation of this safe, clinically proven drug for the management of this devastating gynecologic malignancy. Mol Cancer Ther; 11(8); 1703–12. ©2012 AACR.
