کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
4304074 1288495 2008 7 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Valproic Acid Induces Notch1 Signaling in Small Cell Lung Cancer Cells 1
موضوعات مرتبط
علوم پزشکی و سلامت پزشکی و دندانپزشکی عمل جراحی
پیش نمایش صفحه اول مقاله
Valproic Acid Induces Notch1 Signaling in Small Cell Lung Cancer Cells 1
چکیده انگلیسی

BackgroundSmall cell lung cancer (SCLC) is an aggressive malignancy. Current treatments yield dismal survival rates. We have previously demonstrated that histone deacetylase (HDAC) inhibitors can inhibit neuroendocrine tumor growth. Activation of the Notch1 signaling pathway also impairs SCLC cell viability. In this study, we investigated the ability of the HDAC inhibitor valproic acid (VPA) to activate Notch1 signaling and inhibit proliferation in SCLC cells.Materials and methodsDMS53 human SCLC cells were treated with VPA (0–10 mm) for 2 d. Light microscopy was used to examine changes in cell morphology. Western analysis was performed using antibodies against various Notch1 pathway proteins to assess Notch1 activation. Additionally, immunoblotting was performed for two neuroendocrine tumor markers, chromogranin A and achaete-scute complex-like 1. Finally, a cell proliferation assay was used to measure the effects of VPA on SCLC growth over 8 d.ResultsAfter treatment with VPA, DMS53 cells underwent dramatic changes in morphology. VPA induced expression of the full-length and active forms of Notch1 protein. Furthermore, VPA suppressed levels of neuroendocrine tumor markers chromogranin A and ASLC-1. Importantly, VPA treatment led to dose-dependent inhibition of SCLC cell proliferation.ConclusionsThe HDAC inhibitor VPA activates Notch1 signaling in SCLC cells. VPA induces changes in cell morphology and suppresses neuroendocrine tumor markers, indicating a change in phenotype. Additionally, VPA profoundly inhibits SCLC cell growth. These results suggest that VPA has potential as a novel therapeutic agent for SCLC.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Journal of Surgical Research - Volume 148, Issue 1, July 2008, Pages 31–37
نویسندگان
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