Hesperetin, a potential therapy for carcinoid cancer. Am J Surg 2011 Mar;201(3):329-32; discussion 333
Date
03/04/2011Pubmed ID
21367373Pubmed Central ID
PMC3073682DOI
10.1016/j.amjsurg.2010.08.018Scopus ID
2-s2.0-79952174816 (requires institutional sign-in at Scopus site) 58 CitationsAbstract
BACKGROUND: The investigators' laboratory has demonstrated that the Notch1 signaling pathway acts as a tumor suppressor in carcinoid tumors. The aim of this study was to examine hesperetin, a flavonoid, as a potential Notch1 activator and carcinoid tumor suppressor.
METHODS: A high-throughput drug screen revealed hesperetin as a Notch1 activator. Human gastrointestinal carcinoid (BON) cell growth after hesperetin treatment was assessed with a 3-(4,5-dimethylthiazole-2-yl)-2,5-diphenyl tetrazolium bromide assay. Western blots were used to measure neuroendocrine tumor markers, human achaete-scute complex-like 1, and chromogranin A. Notch1 expression was measured using western blot analysis and real-time polymerase chain reaction.
RESULTS: Hesperetin induced cell death in a dose-dependent manner and reduced achaete-scute complex-like 1 and chromogranin A expression, with a concomitant rise in Notch1 levels. It also induced Notch1 messenger ribonucleic acid, indicating regulation at the transcriptional level.
CONCLUSION: Hesperetin induces Notch1 expression in carcinoid cells, subsequently suppressing tumor cell proliferation and bioactive hormone production. This provides evidence for further study into hesperetin as a potential treatment for carcinoid cancer.
Author List
Zarebczan B, Pinchot SN, Kunnimalaiyaan M, Chen HMESH terms used to index this publication - Major topics in bold
Antineoplastic AgentsBiomarkers, Tumor
Blotting, Western
Carcinoid Tumor
Cell Line, Tumor
Cell Proliferation
Down-Regulation
Gene Expression Regulation, Neoplastic
Hesperidin
Humans
Polymerase Chain Reaction
Receptor, Notch1
Signal Transduction
Stomach Neoplasms
Transcriptional Activation
Up-Regulation
