Genomes and Genes
Affiliation: Texas A and M University
- Moore R, Fritz W, Schneider A, Lin T, Branam A, Safe S, et al. 2,3,7,8-Tetrachlorodibenzo-p-dioxin has both pro-carcinogenic and anti-carcinogenic effects on neuroendocrine prostate carcinoma formation in TRAMP mice. Toxicol Appl Pharmacol. 2016;305:242-249 pubmed publisher..Thus, we demonstrate, for the first time, that ligand-dependent activation of the AHR can alter prostate cancer incidence. The nature of the responses depended on the timing of AHR activation and ligand structures. ..
- Kolluri S, Jin U, Safe S. Role of the aryl hydrocarbon receptor in carcinogenesis and potential as an anti-cancer drug target. Arch Toxicol. 2017;91:2497-2513 pubmed publisher..This review describes the anti-cancer activities of AhR ligands and demonstrates that it is time to separate the AhR from TCDD and exploit the potential of the AhR as a novel target for cancer chemotherapy. ..
- Safe S, Abdelrahim M. Sp transcription factor family and its role in cancer. Eur J Cancer. 2005;41:2438-48 pubmed..Sp/KLF proteins are also potential targets for cancer chemotherapy. ..
- Jin U, Lee S, Pfent C, Safe S. The aryl hydrocarbon receptor ligand omeprazole inhibits breast cancer cell invasion and metastasis. BMC Cancer. 2014;14:498 pubmed publisher..AHR-active pharmaceuticals such as omeprazole that decrease breast cancer cell invasion and metastasis may have important clinical applications for late stage breast cancer chemotherapy. ..
- Safe S, Kasiappan R. Natural Products as Mechanism-based Anticancer Agents: Sp Transcription Factors as Targets. Phytother Res. 2016;30:1723-1732 pubmed publisher..Copyright © 2016 John Wiley & Sons, Ltd. ..
- Hedrick E, Li X, Safe S. Penfluridol Represses Integrin Expression in Breast Cancer through Induction of Reactive Oxygen Species and Downregulation of Sp Transcription Factors. Mol Cancer Ther. 2017;16:205-216 pubmed publisher..Mol Cancer Ther; 16(1); 205-16. Â©2016 AACR. ..
- Cheng Y, Jin U, Davidson L, Chapkin R, Jayaraman A, Tamamis P, et al. Editor's Highlight: Microbial-Derived 1,4-Dihydroxy-2-naphthoic Acid and Related Compounds as Aryl Hydrocarbon Receptor Agonists/Antagonists: Structure-Activity Relationships and Receptor Modeling. Toxicol Sci. 2017;155:458-473 pubmed publisher..We also used computational analysis to show that 1,4-DHNA and TCDD share similar interactions within the AhR binding pocket and differ primarily due to the negatively charged group of 1,4-DHNA. ..
- Lacey A, Rodrigues Hoffman A, Safe S. PAX3-FOXO1A Expression in Rhabdomyosarcoma Is Driven by the Targetable Nuclear Receptor NR4A1. Cancer Res. 2017;77:732-741 pubmed publisher..Taken together, our results provide a preclinical rationale for the use of NR4A1 small-molecule antagonists to treat ARMS and other rhabdomyosarcomas driven by PAX3-FOXO1A. Cancer Res; 77(3); 732-41. Â©2016 AACR. ..
- Nair V, Sreevalsan S, Basha R, Abdelrahim M, Abudayyeh A, Rodrigues Hoffman A, et al. Mechanism of metformin-dependent inhibition of mammalian target of rapamycin (mTOR) and Ras activity in pancreatic cancer: role of specificity protein (Sp) transcription factors. J Biol Chem. 2014;289:27692-701 pubmed publisher..Thus, the antineoplastic activities of metformin in pancreatic cancer are due, in part, to down-regulation of Sp TFs and Sp-regulated IGF-1R and EGFR, which in turn results in inhibition of mTOR and Ras signaling, respectively. ..
- Chintharlapalli S, Papineni S, Lei P, Pathi S, Safe S. Betulinic acid inhibits colon cancer cell and tumor growth and induces proteasome-dependent and -independent downregulation of specificity proteins (Sp) transcription factors. BMC Cancer. 2011;11:371 pubmed publisher..These results suggest that the anticancer activity of BA in colon cancer cells is due, in part, to downregulation of Sp1, Sp3 and Sp4 transcription factors; however, the mechanism of this response is cell context-dependent. ..
- Jin U, Cheng Y, Park H, Davidson L, Callaway E, Chapkin R, et al. Short Chain Fatty Acids Enhance Aryl Hydrocarbon (Ah) Responsiveness in Mouse Colonocytes and Caco-2 Human Colon Cancer Cells. Sci Rep. 2017;7:10163 pubmed publisher..These results demonstrate SCFA-AhR ligand interactions in YAMC and Caco-2 cells where SCFAs synergistically enhance basal and ligand-induced expression of AhR-responsive genes. ..
- Safe S. Carbidopa: a selective Ah receptor modulator (SAhRM). Biochem J. 2017;474:3763-3765 pubmed publisher..These results are consistent with activities of other AhR-active compounds that inhibit carcinogenesis. Like carbidopa, these chemicals are selective AhR modulators with potential clinical applications that are AhR-dependent...
- Karki K, Hedrick E, Kasiappan R, Jin U, Safe S. Piperlongumine Induces Reactive Oxygen Species (ROS)-Dependent Downregulation of Specificity Protein Transcription Factors. Cancer Prev Res (Phila). 2017;10:467-477 pubmed publisher..i>Cancer Prev Res; 10(8); 467-77. Â©2017 AACR. ..
- Cheng Y, Jin U, Allred C, Jayaraman A, Chapkin R, Safe S. Aryl Hydrocarbon Receptor Activity of Tryptophan Metabolites in Young Adult Mouse Colonocytes. Drug Metab Dispos. 2015;43:1536-43 pubmed publisher..These results suggest that the tryptophan metabolites identified in microbiota are selective AhR modulators. ..
- Abdelrahim M, Safe S. Cyclooxygenase-2 inhibitors decrease vascular endothelial growth factor expression in colon cancer cells by enhanced degradation of Sp1 and Sp4 proteins. Mol Pharmacol. 2005;68:317-29 pubmed..These results suggest that the antiangiogenic activity of COX-2 inhibitors in colon cancer cells is linked to activation of proteasome-dependent degradation of Sp1 and Sp4 proteins. ..
- Safe S, Wormke M, Samudio I. Mechanisms of inhibitory aryl hydrocarbon receptor-estrogen receptor crosstalk in human breast cancer cells. J Mammary Gland Biol Neoplasia. 2000;5:295-306 pubmed