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.
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. Humangastrointestinal 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, humanachaete-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.
Authors: Scott N Pinchot; Renata Jaskula-Sztul; Li Ning; Noel R Peters; Mackenzie R Cook; Muthusamy Kunnimalaiyaan; Herbert Chen Journal: Cancer Date: 2010-11-08 Impact factor: 6.860
Authors: David Yu Greenblatt; Max A Cayo; Joel T Adler; Li Ning; Megan R Haymart; Muthusamy Kunnimalaiyaan; Herbert Chen Journal: Ann Surg Date: 2008-06 Impact factor: 12.969
Authors: Jaiprakash R Patil; K N Chidambara Murthy; G K Jayaprakasha; Mahadev B Chetti; Bhimanagouda S Patil Journal: J Agric Food Chem Date: 2009-11-25 Impact factor: 5.279
Authors: Scott N Pinchot; Joel T Adler; Yinggang Luo; Jianhua Ju; Wenli Li; Ben Shen; Muthusamy Kunnimalaiyaan; Herbert Chen Journal: Am J Surg Date: 2009-03 Impact factor: 2.565
Authors: Mackenzie R Cook; Scott N Pinchot; Renata Jaskula-Sztul; Jie Luo; Muthusamy Kunnimalaiyaan; Herbert Chen Journal: Mol Cancer Ther Date: 2010-01-26 Impact factor: 6.261
Authors: Jocelyn F Burke; Logan Schlosser; April D Harrison; Muthusamy Kunnimalaiyaan; Herbert Chen Journal: Ann Surg Oncol Date: 2013-07-31 Impact factor: 5.344
Authors: Jason Whitt; Won S Hong; Rahul R Telange; Chee Paul Lin; James Bibb; David J Beebe; Herbert Chen; Renata Jaskula-Sztul Journal: Cancer Gene Ther Date: 2020-02-07 Impact factor: 5.987