Expression of sulfotransferase SULT1A1 in cancer cells predicts susceptibility to the novel anticancer agent NSC-743380
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Xiao Huang1,*, Mengru Cao1,7,*, Li Wang1, Shuhong Wu1, Xiaoying Liu1, Hongyu Li1, Hui Zhang1, Rui-Yu Wang2, Xiaoping Sun3, Caimiao Wei4, Keith A. Baggerly5, Jack A. Roth1, Michael Wang6, Stephen G. Swisher1 and Bingliang Fang1
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
Bingliang Fang, email:
Keywords: Cancer, drug development, biomarker, sulfotransferase, SULT1A1, personalized therapy
Received: September 05, 2014 Accepted: November 15, 2014 Published: November 16, 2014
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.
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