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.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 345-354 |
| Number of pages | 10 |
| Journal | Oncotarget |
| Volume | 6 |
| Issue number | 1 |
| DOIs | |
| State | Published - 2015 |
Keywords
- Biomarker
- Cancer
- Drug development
- Personalized therapy
- SULT1A1
- Sulfotransferase
ASJC Scopus subject areas
- Oncology
MD Anderson CCSG core facilities
- Advanced Technology Genomics Core
- Bioinformatics Shared Resource
- Biostatistics Resource Group
- Flow Cytometry and Cellular Imaging Facility
- Functional Genomics Core
- Cytogenetics and Cell Authentication Core