The Endocannabinoid System as a Target for Treatment of Breast Cancer

Abstract

During this project period, we employed in vivo and in vitro approaches to determine whether the endogenous cannabinoid system can be targeted to treat breast cancer. The first objective of this work was to develop a preclinical model to induce mammary tumors in mice and determine whether elevating levels of the endogenous cannabinoid anandamide through the use of mice lacking fatty acid amide hydrolase (FAAH), the primary catabolic enzyme responsible for degrading this endogenous cannabinoid, would show decreased tumorigenesis. The carcinogen, DMBA, produced the appearance of tumors in the mammary region of female control C57Bl/6 mice and FAAH knockout mice. However, the tumors could not be conclusively identified as being breast cancer. The second objective of this project was to evaluate interactions of cannabinoids with radiation in MCF-7, MDA-MB-231, and 4T1 breast tumor cell lines. Interestingly, the high efficacy synthetic cannabinoid agonist WIN55,212-2, but not its stereoisomer WIN55,212-3 or the phytocannabinoids 9-tetrahydrocannabinol (THC) or cannabidiol (CBD), significantly enhanced the effects of radiation in decreasing cell viability. The enhanced effects of combination of WIN55,212-2 and radiation on breast cancer suggest the possibility that this type of strategy many hold promise to treat this disease.

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Document Details

Document Type
Technical Report
Publication Date
Aug 01, 2011
Accession Number
ADA558526

Entities

People

  • Aron Lichtman

Organizations

  • Virginia Commonwealth University

Tags

DTIC Thesaurus Topics

  • Alcohols
  • Breast Cancer
  • Cancer
  • Cell Line
  • Cell Physiological Processes
  • Cells
  • Chemotherapy
  • Culture Techniques
  • Department Of Defense
  • Drug Abuse
  • Fatty Acids
  • Indicator Dyes
  • Ionizing Radiation
  • Medical Personnel
  • Neoplasms
  • Therapy
  • Tumor Cell Line

Fields of Study

  • Medicine

Readers

  • Breast cancer cell signaling and growth regulation.
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  • Molecular Biology and Genetics