2. Academic Validation
  3. Serotonin Analogues as Inhibitors of Breast Cancer Cell Growth

Serotonin Analogues as Inhibitors of Breast Cancer Cell Growth

  • ACS Med Chem Lett. 2017 Sep 14;8(10):1072-1076. doi: 10.1021/acsmedchemlett.7b00282.
Jiney Jose 1 2,  Clint D J Tavares 1 3,  Nancy D Ebelt 1 3,  Alessia Lodi 4,  Ramakrishna Edupuganti 1 2,  Xuemei Xie 5 6,  Ashwini K Devkota 1 3,  Tamer S Kaoud 1,  Carla L Van Den Berg 3 7,  Eric V Anslyn 2,  Stefano Tiziani 4,  Chandra Bartholomeusz 5 6,  Kevin N Dalby 1 3
Affiliations

Affiliations

  • 1 Division of Chemical Biology and Medicinal Chemistry, College of Pharmacy, University of Texas at Austin, Austin, Texas 78712, United States.
  • 2 Department of Chemistry, University of Texas at Austin, Austin, Texas 78712, United States.
  • 3 Graduate Program in Cell and Molecular Biology, University of Texas at Austin, Austin, Texas 78712, United States.
  • 4 Department of Nutritional Sciences, Dell Pediatric Research Institute, University of Texas at Austin, Austin, Texas 78723, United States.
  • 5 Section of Translational Breast Cancer Research, University of Texas MD Anderson Cancer Center, Houston, Texas 77030, United States.
  • 6 Department of Breast Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas 77030, United States.
  • 7 Division of Pharmacology & Toxicology, College of Pharmacy, University of Texas at Austin, Dell Pediatric Research Institute, Austin, Texas 78723, United States.
PMID: 29057053 DOI: 10.1021/acsmedchemlett.7b00282
Abstract

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.

Keywords

Breast cancer; serotonin receptor; tryptamine.

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