Title:Targeting Heme for the Identification of Cytotoxic Agents
VOLUME: 13 ISSUE: 3
Author(s):Shiming Zhang, Hui Chen, Jessica Webster and Glenn S. Gerhard
Affiliation:Department of Biochemistry and Molecular Biology, Pennsylvania State University, College of Medicine, 500 University Drive, Hershey, PA 17033, USA.
Keywords:Heme, Target, Cancer, High-throughput screen, Cytotoxicity
Abstract:Certain tumor types have an increased capacity for heme synthesis, which serves as the basis for photodynamic therapy. Heme
also serves as the target for the anti-malaria drug artemisinin, which has also been used as an anti-cancer drug. We developed a highthroughput
screening assay to identify heme interacting (HI) compounds, which included imidazole, pyridine, carbonitrile, isocyanide,
and quinoline core structures that are known to interact with heme or hemin. The cytotoxicity of several of the compounds towards
human leukemia cell lines could be modulated by increasing or decreasing heme synthesis. Spectral analysis indicated that distinct
molecular interactions occurred with heme, suggesting that HI compounds appear to target heme with exquisite specificity. These studies
suggest that heme may serve as a novel therapeutic target for cancer drug discovery.
