Hesperetin, a potential therapy for carcinoid cancer

Abstract

Background 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. Methods 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. Results 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. 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. Summary A retrospective review of patients with thin melanoma to determine factors associated with a positive sentinel lymph node from a single institution.

Neuroprotective effect of water-dispersible hesperetin in retinal ischemia reperfusion injury

“…It is reported that Hpt has various beneficial effects including anti-oxidative [18], anti-inflammatory [19], anti-viral [20] and anti-carcinogenic [21] [22]. In addition, a recent experimental study demonstrates that Hpt can also prevent diabetes-induced gliosis, and vascular permeability in the retina [23].…”

Effect of hesperetin on tyrosinase: Inhibition kinetics integrated computational simulation study

“…Hesperetin occurs ubiquitously in citrus fruits as hesperidin (its glycoside form), which acts as a prodrug [22]. Hesperetin has biological and pharmacological activities including antioxidant, anti-inflammatory, anticarcinogenic, antihypertensive and anti-atherogenic properties [23][24][25]. Hesperetin is ingested from the hesperidin by breaking glycosidic bond with releasing glycone.…”

Gastroenteropancreatic neuroendocrine tumors: new insights in the diagnosis and therapy

“…Following the demonstration that the Notch 1 signaling pathway acts as a tumor suppressor gene in carcinoid tumors the flavonoid herceptin, a potential Notch 1 activator, has been used as a therapeutic mean. Herceptin induced Notch 1 expression in carcinoid tumors leading to suppression of tumor cell proliferation and bioactive hormone production, thus providing evidence of its activity in such tumors [41].…”