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

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.

• Authors: Xiao Huang, Mengru Cao, Li Wang, Shuhong Wu, Xiaoying Liu, Hongyu Li, Hui Zhang, Rui-Yu Wang, Xiaoping Sun, Caimiao Wei, Keith A Baggerly, Jack A Roth, Michael Wang, Stephen G Swisher, Bingliang Fang
• Journal: Oncotarget (Oncotarget) Vol. 6 Issue 1 Pg. 345-54 (Jan 01 2015) ISSN: 1949-2553 [Electronic] United States
• PMID: 25514600 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)

Chemical References

• 1-((3-chlorophenyl)methyl)-1H-indole-3-carbinol
• Antineoplastic Agents
• Biomarkers, Tumor
• Indoles
• Arylsulfotransferase
• SULT1A1 protein, human

Topics

• Antineoplastic Agents (pharmacology)
• Arylsulfotransferase (biosynthesis)
• Biomarkers, Tumor (analysis)
• Blotting, Western
• Cell Line, Tumor (drug effects, enzymology)
• Cell Survival (drug effects)
• Drug Screening Assays, Antitumor
• Humans
• Indoles (pharmacology)
• Real-Time Polymerase Chain Reaction
• Transfection