| Morphine suppresses tumor angiogenesis through a HIF-1alpha/p38MAPK pathway. | |
| | |
MedLine Citation:
|
PMID: 20616349 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
|
Morphine, a highly potent analgesic agent, is frequently prescribed for moderate to severe cancer pain. In this study, morphine was administered at a clinically relevant analgesic dose to assess tumor cell-induced angiogenesis and subcutaneous tumor growth in nude mice using mouse Lewis lung carcinoma cells (LLCs). Implantation of mice with a continuous slow-release morphine pellet achieved morphine plasma levels within 250-400 ng/ml (measured using a radioimmunoassay, Coat-A-Count Serum Morphine) and was sufficient to significantly reduce tumor cell-induced angiogenesis and tumor growth when compared with placebo treatment. Morphometric analysis for blood vessel formation further confirmed that morphine significantly reduced blood vessel density (P < 0.003), vessel branching (P < 0.05), and vessel length (P < 0.002) when compared with placebo treatment. Morphine's effect was abolished in mice coadministered the classical opioid receptor antagonist, naltrexone, and in mu-opioid receptor knockout mice, supporting the involvement of the classical opioid receptors in vivo. Morphine's inhibitory effect is mediated through the suppression of the hypoxia-induced mitochondrial p38 mitogen-activated protein kinase (MAPK) pathway. Our results suggest that in vitro morphine treatment of LLCs inhibits the hypoxia-induced nuclear translocation of hypoxia-inducible transcription factor 1alpha to reduce vascular endothelial growth factor transcription and secretion, in a manner similar to pharmacological blockade with the p38 MAPK-specific inhibitor, SB203585. These studies indicate that morphine, in addition to its analgesic function, may be exploited for its antiangiogenic potential. |
| | |
Authors:
|
Lisa Koodie; Sundaram Ramakrishnan; Sabita Roy |
Related Documents
:
|
8791129 - Tumor angiogenesis and the role of vascular cell integrin alphavbeta3. 21858709 - Influence of the vascular damaging agents dmxaa and zd6126 on hypericin distribution an... 20308559 - P53-induced microrna-107 inhibits hif-1 and tumor angiogenesis. 10928819 - Vitamin d analogs in cutaneous malignancies. 18688849 - Oral cancer overexpressed 1 (oraov1): a regulator for the cell growth and tumor angioge... 2417679 - Inhibition of tumor angiogenesis by hexuronyl hexosaminoglycan sulfate. 1057449 - Growth rate of pulmonary metastases in human sarcomas. 22149139 - Enhancement of the targeting capabilities of the paclitaxel-loaded pluronic nanoparticl... 16301719 - Contrast-enhanced ultrasonography in the diagnosis of solid renal tumors. |
Publication Detail:
|
Type: Journal Article; Research Support, N.I.H., Extramural Date: 2010-07-08 |
Journal Detail:
|
Title: The American journal of pathology Volume: 177 ISSN: 1525-2191 ISO Abbreviation: Am. J. Pathol. Publication Date: 2010 Aug |
Date Detail:
|
Created Date: 2010-08-03 Completed Date: 2011-01-25 Revised Date: 2012-01-09 |
Medline Journal Info:
|
Nlm Unique ID: 0370502 Medline TA: Am J Pathol Country: United States |
Other Details:
|
Languages: eng Pagination: 984-97 Citation Subset: AIM; IM |
Affiliation:
|
Department of Pharmacology, University of Minnesota Medical School, Minneapolis, MN 55455, USA. |
Export Citation:
|
APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
|
Analgesics, Opioid*
/
pharmacology,
therapeutic use Animals Anoxia / metabolism Cell Line, Tumor Enzyme Activation Humans Hypoxia-Inducible Factor 1, alpha Subunit / metabolism* Lung Neoplasms / metabolism, pathology Mice Mice, Knockout Mice, Nude Morphine* / pharmacology, therapeutic use Neoplasm Transplantation Neovascularization, Pathologic* / drug therapy, metabolism Receptors, Opioid, mu / genetics, metabolism Signal Transduction / drug effects* p38 Mitogen-Activated Protein Kinases / metabolism* |
| Grant Support | |
ID/Acronym/Agency:
|
CA114340/CA/NCI NIH HHS; F31-DA021005-01/DA/NIDA NIH HHS; K02 DA015349-10/DA/NIDA NIH HHS; KO2 DA 015349/DA/NIDA NIH HHS; P50 DA 011806/DA/NIDA NIH HHS; R01 CA114340-05/CA/NCI NIH HHS; R01 DA 022935/DA/NIDA NIH HHS; R01 DA 12104/DA/NIDA NIH HHS; R01 DA012104-13/DA/NIDA NIH HHS |
| Chemical | |
Reg. No./Substance:
|
0/Analgesics, Opioid; 0/Hypoxia-Inducible Factor 1, alpha Subunit; 0/Receptors, Opioid, mu; 57-27-2/Morphine; EC 2.7.11.24/p38 Mitogen-Activated Protein Kinases |
| Comments/Corrections | |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
Previous Document: Therapeutic effects of vitamin D analogs on cardiac hypertrophy in spontaneously hypertensive rats.
Next Document: Clues Emerge on How HIV Increases Lymphoma Risk.