Dopamine Blocks Stress-Mediated Ovarian Carcinoma Growth

Myrthala MORENO-SMITH; Chunhua Lu; Gabriel LOPEZ BERESTEIN; Steve W COLE; Susan K LUTGENDORF; Anil K SOOD; Mian M. K SHAHZAD; Guillermo N ARMAIZ PENA; Julie K ALLEN; Rebecca L STONE; Lingegowda S MANGALA; Hee Dong Han; Hye Sun Kim; Donna FARLEY

doi:10.1158/1078-0432.CCR-10-2441

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Dopamine Blocks Stress-Mediated Ovarian Carcinoma Growth

Journal article

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Dopamine Blocks Stress-Mediated Ovarian Carcinoma Growth

Myrthala MORENO-SMITH, Chunhua Lu, Gabriel LOPEZ BERESTEIN, Steve W COLE, Susan K LUTGENDORF, Anil K SOOD, Mian M. K SHAHZAD, Guillermo N ARMAIZ PENA, Julie K ALLEN, Rebecca L STONE, …

Clinical cancer research, Vol.17(11), pp.3649-3659

2011

DOI: 10.1158/1078-0432.CCR-10-2441

PMCID: PMC3107884

PMID: 21531818

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Abstract

Purpose: Increased adrenergic activity in response to chronic stress is known to promote tumor growth by stimulating the tumor microenvironment. The focus of the current study was to determine whether dopamine, an inhibitory catecholamine, could block the effects of chronic stress on tumor growth. Experimental Design: Expression of dopamine receptors (DR1–DR5) was analyzed by reverse transcriptase-PCR and by Western blotting. In vitro effects of dopamine on cell viability, apoptosis, and migration were examined. For in vivo therapy, murine and human DR2-siRNAs were incorporated into chitosan nanoparticles (CH-NP). Results: In this model of chronic stress, tumoral norepinephrine levels remained elevated whereas dopamine levels were significantly decreased compared with nonstressed animals. Daily restraint stress resulted in significantly increased tumor growth in both immunodeficient (SKOV3ip1 and HeyA8) and immunocompetent (ID8) ovarian cancer models. This increase was completely blocked with daily dopamine treatment. Dopamine treatment also blocked the stress-induced increase in angiogenesis. Endothelial and ovarian cancer cells expressed all dopamine receptors except for the lack of DR3 expression in ovarian cancer cells. DR2 was responsible for the inhibitory effects of dopamine on tumor growth and microvessel density as well as the stimulatory effect on apoptosis, as the DR2 antagonist eticlopride reversed these effects. Dopamine significantly inhibited cell viability and stimulated apoptosis in vitro. Moreover, dopamine reduced cyclic AMP levels and inhibited norepinephrine and vascular permeability factor/VEGF-induced Src kinase activation. Conclusions: Dopamine depletion under chronic stress conditions creates a permissive microenvironment for tumor growth that can be reversed by dopamine replacement

Antineoplastic Agents

Tumors

Gynecology. Andrology. Obstetrics

Pharmacology. Drug treatments

Biological and medical sciences

Medical sciences

Female genital diseases

Details

Title: Subtitle: Dopamine Blocks Stress-Mediated Ovarian Carcinoma Growth
Creators: Myrthala MORENO-SMITH - Department of Gynecologic Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas, United States
Chunhua Lu - Department of Gynecologic Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas, United States
Gabriel LOPEZ BERESTEIN - Department of Cancer Biology, University of Texas MD Anderson Cancer Center, Houston, Texas, United States
Steve W COLE - Department of Medicine, Division of Hematology-Oncology, UCLA School of Medicine, Los Angeles, California, United States
Susan K LUTGENDORF - Departments of Psychology and Gynecology and the Holden Comprehensive Cancer Center, University of Iowa, Iowa City, Iowa, United States
Anil K SOOD - Department of Gynecologic Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas, United States
Mian M. K SHAHZAD - School of Medicine and Public Health, University of Wisconsin, Madison, Wisconsin, United States
Guillermo N ARMAIZ PENA - Department of Gynecologic Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas, United States
Julie K ALLEN - Department of Gynecologic Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas, United States
Rebecca L STONE - Department of Gynecologic Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas, United States
Lingegowda S MANGALA - Radiation Biophysics Laboratory, NASA Johnson Space Center, University of Space Research Association, Houston, Texas, United States
Hee Dong Han - Department of Gynecologic Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas, United States
Hye Sun Kim - Department of Gynecologic Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas, United States
Donna FARLEY - Institute for Clinical and Translational Science General Hospital-Boyd Tower, Iowa City, Iowa, United States
Resource Type: Journal article
Publication Details: Clinical cancer research, Vol.17(11), pp.3649-3659
DOI: 10.1158/1078-0432.CCR-10-2441
PMID: 21531818
PMCID: PMC3107884
NLM abbreviation: Clin Cancer Res
ISSN: 1078-0432
eISSN: 1557-3265
Publisher: American Association for Cancer Research; Philadelphia, PA
Language: English
Date published: 2011
Academic Unit: Psychological and Brain Sciences; Iowa Neuroscience Institute; Obstetrics and Gynecology; Urology
Record Identifier: 9984065883302771

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