title: Suberoyl bishydroxamic acid inhibits cellular proliferation by inducing cell cycle arrest in carcinoid cancer cells.
abstract: Carcinoid cancers arise from the neuroendocrine cell system of the gastrointestinal tract, lungs, and other organs. Hepatic metastases are common, and patients often suffer from endocrinopathies secondary to tumor secretion of various hormones and peptides. As complete surgical resection is often not possible because of widespread disease, new therapeutic and palliative treatments are needed. In this study, we characterized the effects of suberoyl bishydroxamic acid (SBHA), a histone deacetylase inhibitor, on the growth and neuroendocrine phenotype of carcinoid cancer cells. SBHA treatment of human gastrointestinal and pulmonary carcinoid cancer cells resulted in a dose-dependent inhibition of cell proliferation. Western blot analysis showed a decrease in cyclin D1 and an increase in p21 and p27, indicating that the mechanism of this growth inhibition is cell cycle arrest. Furthermore, SBHA treatment suppressed two neuroendocrine tumor markers, chromogranin A and achaete-scute complex-like 1. These changes in the growth and neuroendocrine phenotype of carcinoid cells were associated with activation of the Notch1 signaling cascade. We conclude that SBHA shows promise as a potential anticancer agent for the treatment of patients with advanced carcinoid tumor disease.
authors.affiliation: Endocrine Surgery Research Laboratories, Department of Surgery, University of Wisconsin, Madison, WI 53792, USA.
authors.forename: David Yu
authors.initials: DY
authors.lastname: Greenblatt
authors.forename: Max
authors.initials: M
authors.lastname: Cayo
authors.forename: Li
authors.initials: L
authors.lastname: Ning
authors.forename: Renata
authors.initials: R
authors.lastname: Jaskula-Sztul
authors.forename: Megan
authors.initials: M
authors.lastname: Haymart
authors.forename: Muthusamy
authors.initials: M
authors.lastname: Kunnimalaiyaan
authors.forename: Herbert
authors.initials: H
authors.lastname: Chen
mesh_terms: D051792:Basic Helix-Loop-Helix Proteins / Q000097:blood; D015153:Blotting, Western; D002276:Carcinoid Tumor / Q000503:physiopathology*; D002453:Cell Cycle / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects*; D053379:Chromogranin A / Q000097:blood; D019938:Cyclin D1 / Q000032:analysis; D006801:Humans; D006877:Hydroxamic Acids / Q000494:pharmacology*; D051881:Receptor, Notch1 / Q000187:drug effects; D014407:Tumor Cells, Cultured
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D053379:Chromogranin A; D019938:Cyclin D1; D006877:Hydroxamic Acids; D051881:Receptor, Notch1; C065500:ASCL1 protein, human