Faculty Collaboration Database

ZM336372, a Raf-1 activator, causes suppression of proliferation in a human hepatocellular carcinoma cell line. J Gastrointest Surg 2008 May;12(5):852-7

Date

02/27/2008

Pubmed ID

18299943

DOI

10.1007/s11605-008-0495-x

Scopus ID

2-s2.0-42449125172 (requires institutional sign-in at Scopus site)   8 Citations

Abstract

Hepatocellular carcinoma has been described to exhibit characteristics similar to that of neuroendocrine tumors (NETs). This includes similar anti-neoplastic responses to extracellular signal-regulated kinase (ERK) activation. NET cells and HepG2 cells have both shown growth inhibition with ERK activation. ZM336372, a Raf-1 activating agent, has been shown to cause growth inhibition and suppression of hormone secretion in a neuroendocrine cell line. Here we examine treatment of the HepG2 cell line with ZM336732 to determine if a similar anti-proliferative response will be obtained. HepG2 cells were treated with ZM336372 or solvent (dimethyl sulfoxide). The resulting effect on the proliferation was measured using the 3,4-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Western blot analysis was performed to examine the activation of the Raf-1/mitogen-activated protein kinase kinase/ERK pathway, chromogranin A production, and p21CIP1 level. Growth inhibition was observed with ZM336372 in a dose-dependent fashion. Minimal baseline phosphorylation of ERK 1/2 was observed; however, activation was observed after treatment with ZM336372. Chromogranin A secretion was suppressed due to treatment with ZM336372. A dose-dependent up-regulation of p21CIP1 was observed in response to ZM336372 treatment. ZM336372 causes growth inhibition, suppression of hormone secretion, and up-regulation of cell cycle inhibitors in a human hepatocellular carcinoma cell line, similar to that previously seen in NETs.

Author List

Deming D, Geiger P, Chen H, Vaccaro A, Kunnimalaiyaan M, Holen K

MESH terms used to index this publication - Major topics in bold

Benzamides
Carcinoma, Hepatocellular
Cell Cycle
Cell Proliferation
Chromogranin A
Cyclin-Dependent Kinase Inhibitor p21
Extracellular Signal-Regulated MAP Kinases
Humans
Liver Neoplasms
Mitogen-Activated Protein Kinase Kinases
Proto-Oncogene Proteins c-raf
Signal Transduction
Tumor Cells, Cultured
Up-Regulation