Serotonin Analogues as Inhibitors of Breast Cancer Cell Growth.

Autor: Jose J; Division of Chemical Biology and Medicinal Chemistry, College of Pharmacy, University of Texas at Austin, Austin, Texas 78712, United States.; Department of Chemistry, University of Texas at Austin, Austin, Texas 78712, United States., Tavares CDJ; Division of Chemical Biology and Medicinal Chemistry, College of Pharmacy, University of Texas at Austin, Austin, Texas 78712, United States.; Graduate Program in Cell and Molecular Biology, University of Texas at Austin, Austin, Texas 78712, United States., Ebelt ND; Division of Chemical Biology and Medicinal Chemistry, College of Pharmacy, University of Texas at Austin, Austin, Texas 78712, United States.; Graduate Program in Cell and Molecular Biology, University of Texas at Austin, Austin, Texas 78712, United States., Lodi A; Department of Nutritional Sciences, Dell Pediatric Research Institute, University of Texas at Austin, Austin, Texas 78723, United States., Edupuganti R; Division of Chemical Biology and Medicinal Chemistry, College of Pharmacy, University of Texas at Austin, Austin, Texas 78712, United States.; Department of Chemistry, University of Texas at Austin, Austin, Texas 78712, United States., Xie X; Section of Translational Breast Cancer Research, University of Texas MD Anderson Cancer Center, Houston, Texas 77030, United States.; Department of Breast Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas 77030, United States., Devkota AK; Division of Chemical Biology and Medicinal Chemistry, College of Pharmacy, University of Texas at Austin, Austin, Texas 78712, United States.; Graduate Program in Cell and Molecular Biology, University of Texas at Austin, Austin, Texas 78712, United States., Kaoud TS; Division of Chemical Biology and Medicinal Chemistry, College of Pharmacy, University of Texas at Austin, Austin, Texas 78712, United States., Van Den Berg CL; Graduate Program in Cell and Molecular Biology, University of Texas at Austin, Austin, Texas 78712, United States.; Division of Pharmacology & Toxicology, College of Pharmacy, University of Texas at Austin, Dell Pediatric Research Institute, Austin, Texas 78723, United States., Anslyn EV; Department of Chemistry, University of Texas at Austin, Austin, Texas 78712, United States., Tiziani S; Department of Nutritional Sciences, Dell Pediatric Research Institute, University of Texas at Austin, Austin, Texas 78723, United States., Bartholomeusz C; Section of Translational Breast Cancer Research, University of Texas MD Anderson Cancer Center, Houston, Texas 77030, United States.; Department of Breast Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas 77030, United States., Dalby KN; Division of Chemical Biology and Medicinal Chemistry, College of Pharmacy, University of Texas at Austin, Austin, Texas 78712, United States.; Graduate Program in Cell and Molecular Biology, University of Texas at Austin, Austin, Texas 78712, United States.
Jazyk: angličtina
Zdroj: ACS medicinal chemistry letters [ACS Med Chem Lett] 2017 Sep 14; Vol. 8 (10), pp. 1072-1076. Date of Electronic Publication: 2017 Sep 14 (Print Publication: 2017).
DOI: 10.1021/acsmedchemlett.7b00282
Abstrakt: Serotonin (5-hydroxytryptamine, 5-HT) is a critical local regulator of epithelial homeostasis in the breast and exerts its actions through a number of receptors. Dysregulation of serotonin signaling is reported to contribute to breast cancer pathophysiology by enhancing cell proliferation and promoting resistance to apoptosis. Preliminary analyses indicated that the potent 5-HT1B/1D serotonin receptor agonist 5-nonyloxytryptamine (5-NT), a triptan-like molecule, induced cell death in breast cancer cell lines. Thus, we synthesized a series of novel alkyloxytryptamine analogues, several of which decreased the viability of various human cancer cell lines. Proteomic and metabolomic analyses showed that compounds 6 and 10 induced apoptosis and interfered with signaling pathways that regulate protein translation and survival, such as the Akt/mTOR pathway, in triple-negative breast cancer cells.
Databáze: MEDLINE