Our laboratory has demonstrated that the Notch1 signaling pathway acts as a tumor suppressor in carcinoids. In this study we examined hesperetin, a flavinoid, as a potential Notch1 activator and carcinoid tumor suppressor.
A high throughput drug screen revealed hesperetin as a Notch1 activator. Human GI carcinoid (BON) cell growth after hesperetin treatment was assessed with a 3-(4,5-Dimethylthiazole-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay. Western blots were used to measure neuroendocrine tumor markers, human achaete-scute complex-like 1 (ASCL1) and chromogranin A (CgA). Notch1 expression was measured using western blot analysis and real-time PCR.
Hesperetin induces cell death in a dose dependent manner and reduces ASCL1 and CgA expression with a concomitant rise in Notch1 levels. It also induces Notch1 mRNA, indicating regulation at the transcriptional level.
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.
A retrospective review of patients with thin melanoma to determine factors associated with a positive sentinel lymph node from a single institution.
Keywords: carcinoid tumors, Notch1 signaling pathway, hesperetin