ZM336372, a Raf-1 activator, suppresses growth and neuroendocrine hormone levels in carcinoid tumor cells

Jamie Van Gompel, Muthusamy Kunnimalaiyaan, Kyle Holen, Herbert Chen

Research output: Contribution to journalArticle

58 Citations (Scopus)

Abstract

Neuroendocrine tumors, such as carcinoids, are highly metastatic neoplasms that secrete bioactive hormones resulting in carcinoid syndrome. Few curative treatments exist outside of surgical resection. We have previously shown that activation of the Raf-1 signaling pathway can suppress hormone production in carcinoid tumor cells. In this study, we investigated a novel treatment for carcinoid tumor cell growth based on pharmacologic Raf-1 activation using the compound ZM336372. Treatment of carcinoid tumor cells with ZM336372 resulted in progressive phosphorylation of Raf-1, mitogen-activated protein kinase 1/2, and extracellular signal-regulated kinase 1/2. Importantly, exposure to ZM336372 resulted in a significant reduction of bioactive hormone levels as well as the transcription factor, human achaete-scute homologue-1 in carcinoid tumor cells. Furthermore, treatment with ZM336372 led to a marked suppression of cellular proliferation and induction of the cell cycle inhibitors p21 and p18. In summary, ZM336372 targets both proliferation and palliative issues associated with carcinoid tumor cells, and therefore, warrants further investigation as a possible therapeutic strategy for patients with carcinoid tumors.

Original languageEnglish (US)
Pages (from-to)910-917
Number of pages8
JournalMolecular Cancer Therapeutics
Volume4
Issue number6
DOIs
StatePublished - Jun 2005
Externally publishedYes

Fingerprint

Carcinoid Tumor
Growth Hormone
Mitogen-Activated Protein Kinase 1
Hormones
Therapeutics
Mitogen-Activated Protein Kinase 3
Neuroendocrine Tumors
N-(5-(3-dimethylaminobenzamido)-2-methylphenyl)-4-hydroxybenzamide
Cell Cycle
Transcription Factors
Phosphorylation
Cell Proliferation
Growth

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

ZM336372, a Raf-1 activator, suppresses growth and neuroendocrine hormone levels in carcinoid tumor cells. / Van Gompel, Jamie; Kunnimalaiyaan, Muthusamy; Holen, Kyle; Chen, Herbert.

In: Molecular Cancer Therapeutics, Vol. 4, No. 6, 06.2005, p. 910-917.

Research output: Contribution to journalArticle

Van Gompel, Jamie ; Kunnimalaiyaan, Muthusamy ; Holen, Kyle ; Chen, Herbert. / ZM336372, a Raf-1 activator, suppresses growth and neuroendocrine hormone levels in carcinoid tumor cells. In: Molecular Cancer Therapeutics. 2005 ; Vol. 4, No. 6. pp. 910-917.
@article{c264d04ed0af4bb3aaccedf27df548ae,
title = "ZM336372, a Raf-1 activator, suppresses growth and neuroendocrine hormone levels in carcinoid tumor cells",
abstract = "Neuroendocrine tumors, such as carcinoids, are highly metastatic neoplasms that secrete bioactive hormones resulting in carcinoid syndrome. Few curative treatments exist outside of surgical resection. We have previously shown that activation of the Raf-1 signaling pathway can suppress hormone production in carcinoid tumor cells. In this study, we investigated a novel treatment for carcinoid tumor cell growth based on pharmacologic Raf-1 activation using the compound ZM336372. Treatment of carcinoid tumor cells with ZM336372 resulted in progressive phosphorylation of Raf-1, mitogen-activated protein kinase 1/2, and extracellular signal-regulated kinase 1/2. Importantly, exposure to ZM336372 resulted in a significant reduction of bioactive hormone levels as well as the transcription factor, human achaete-scute homologue-1 in carcinoid tumor cells. Furthermore, treatment with ZM336372 led to a marked suppression of cellular proliferation and induction of the cell cycle inhibitors p21 and p18. In summary, ZM336372 targets both proliferation and palliative issues associated with carcinoid tumor cells, and therefore, warrants further investigation as a possible therapeutic strategy for patients with carcinoid tumors.",
author = "{Van Gompel}, Jamie and Muthusamy Kunnimalaiyaan and Kyle Holen and Herbert Chen",
year = "2005",
month = "6",
doi = "10.1158/1535-7163.MCT-04-0334",
language = "English (US)",
volume = "4",
pages = "910--917",
journal = "Molecular Cancer Therapeutics",
issn = "1535-7163",
publisher = "American Association for Cancer Research Inc.",
number = "6",

}

TY - JOUR

T1 - ZM336372, a Raf-1 activator, suppresses growth and neuroendocrine hormone levels in carcinoid tumor cells

AU - Van Gompel, Jamie

AU - Kunnimalaiyaan, Muthusamy

AU - Holen, Kyle

AU - Chen, Herbert

PY - 2005/6

Y1 - 2005/6

N2 - Neuroendocrine tumors, such as carcinoids, are highly metastatic neoplasms that secrete bioactive hormones resulting in carcinoid syndrome. Few curative treatments exist outside of surgical resection. We have previously shown that activation of the Raf-1 signaling pathway can suppress hormone production in carcinoid tumor cells. In this study, we investigated a novel treatment for carcinoid tumor cell growth based on pharmacologic Raf-1 activation using the compound ZM336372. Treatment of carcinoid tumor cells with ZM336372 resulted in progressive phosphorylation of Raf-1, mitogen-activated protein kinase 1/2, and extracellular signal-regulated kinase 1/2. Importantly, exposure to ZM336372 resulted in a significant reduction of bioactive hormone levels as well as the transcription factor, human achaete-scute homologue-1 in carcinoid tumor cells. Furthermore, treatment with ZM336372 led to a marked suppression of cellular proliferation and induction of the cell cycle inhibitors p21 and p18. In summary, ZM336372 targets both proliferation and palliative issues associated with carcinoid tumor cells, and therefore, warrants further investigation as a possible therapeutic strategy for patients with carcinoid tumors.

AB - Neuroendocrine tumors, such as carcinoids, are highly metastatic neoplasms that secrete bioactive hormones resulting in carcinoid syndrome. Few curative treatments exist outside of surgical resection. We have previously shown that activation of the Raf-1 signaling pathway can suppress hormone production in carcinoid tumor cells. In this study, we investigated a novel treatment for carcinoid tumor cell growth based on pharmacologic Raf-1 activation using the compound ZM336372. Treatment of carcinoid tumor cells with ZM336372 resulted in progressive phosphorylation of Raf-1, mitogen-activated protein kinase 1/2, and extracellular signal-regulated kinase 1/2. Importantly, exposure to ZM336372 resulted in a significant reduction of bioactive hormone levels as well as the transcription factor, human achaete-scute homologue-1 in carcinoid tumor cells. Furthermore, treatment with ZM336372 led to a marked suppression of cellular proliferation and induction of the cell cycle inhibitors p21 and p18. In summary, ZM336372 targets both proliferation and palliative issues associated with carcinoid tumor cells, and therefore, warrants further investigation as a possible therapeutic strategy for patients with carcinoid tumors.

UR - http://www.scopus.com/inward/record.url?scp=21344443715&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=21344443715&partnerID=8YFLogxK

U2 - 10.1158/1535-7163.MCT-04-0334

DO - 10.1158/1535-7163.MCT-04-0334

M3 - Article

C2 - 15956248

AN - SCOPUS:21344443715

VL - 4

SP - 910

EP - 917

JO - Molecular Cancer Therapeutics

JF - Molecular Cancer Therapeutics

SN - 1535-7163

IS - 6

ER -