Expression of sulfotransferase SULT1A1 in cancer cells predicts susceptibility to the novel anticancer agent NSC-743380

// Xiao Huang 1,* , Mengru Cao 1,7,* , Li Wang 1 , Shuhong Wu 1 , Xiaoying Liu 1 , Hongyu Li 1 , Hui Zhang 1 , Rui-Yu Wang 2 , Xiaoping Sun 3 , Caimiao Wei 4 , Keith A. Baggerly 5 , Jack A. Roth 1 , Michael Wang 6 , Stephen G. Swisher 1 and Bingliang Fang 1 1 Department of Thoracic and Cardiovascular Surgery, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA 2 Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA 3 Department of Laboratory Medicine, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA 4 Department of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA 5 Department of Bioinformatics and Computation Biology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA 6 Department of Lymphoma, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA 7 The Fourth Department of Medicine Oncology, Harbin Medical University Cancer Hospital, Harbin, China * These authors contributed equally to this work Correspondence: Bingliang Fang, email: // Keywords : Cancer, drug development, biomarker, sulfotransferase, SULT1A1, personalized therapy Received : September 05, 2014 Accepted : November 15, 2014 Published : November 16, 2014 Abstract The small molecule anticancer agent NSC-743380 modulates functions of multiple cancer-related pathways and is highly active in a subset of cancer cell lines in the NCI-60 cell line panel. It also has promising in vivo anticancer activity. However, the mechanisms underlying NSC-743380’s selective anticancer activity remain uncharacterized. To determine biomarkers that may be used to identify responders to this novel anticancer agent, we performed correlation analysis on NSC-743380’s anticancer activity and the gene expression levels in NCI-60 cell lines and characterized the functions of the top associated genes in NSC-743380–mediated anticancer activity. We found sulfotransferase SULT1A1 is causally associated with NSC-743380’s anticancer activity. SULT1A1 was expressed in NSC-743380–sensitive cell lines but was undetectable in resistant cancer cells. Ectopic expression of SULT1A1 in NSC743380 resistant cancer cells dramatically sensitized the resistant cells to NSC-743380. Knockdown of the SULT1A1 in the NSC-743380 sensitive cancer cell line rendered it resistance to NSC-743380. The SULT1A1 protein levels in cell lysates from 18 leukemia cell lines reliably predicted the susceptibility of the cell lines to NSC-743380. Thus, expression of SULT1A1 in cancer cells is required for NSC-743380’s anticancer activity and can be used as a biomarker for identification of NSC-743380 responders.