Down-regulation of cyclooxygenase-2 (COX-2) by cannabidiolic acid in human breast cancer cells

J Toxicol Sci. 2014;39(5):711-6. doi: 10.2131/jts.39.711.

Abstract

Metastases are known to be responsible for approximately 90% of breast cancer-related deaths. Cyclooxygenase-2 (COX-2) is involved not only in inflammatory processes, but also in the metastasis of cancer cells; it is expressed in 40% of human invasive breast cancers. To comprehensively analyze the effects of cannabidiolic acid (CBDA), a selective COX-2 inhibitor found in the fiber-type cannabis plant (Takeda et al., 2008), on COX-2 expression and the genes involved in metastasis, we performed a DNA microarray analysis of human breast cancer MDA-MB-231 cells, which are invasive breast cancer cells that express high levels of COX-2, treated with CBDA for 48 hr at 25 µM. The results obtained revealed that COX-2 and Id-1, a positive regulator of breast cancer metastasis, were down-regulated (0.19-fold and 0.52-fold, respectively), while SHARP1 (or BHLHE41), a suppressor of breast cancer metastasis, was up-regulated (1.72-fold) and CHIP (or STUB1) was unaffected (1.03-fold). These changes were confirmed by real-time RT-PCR analyses. Taken together, the results obtained here demonstrated that i) CBDA had dual inhibitory effects on COX-2 through down-regulation and enzyme inhibition, and ii) CBDA may possess the ability to suppress genes that are positively involved in the metastasis of cancer cells in vitro.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents, Phytogenic
  • Basic Helix-Loop-Helix Transcription Factors / genetics
  • Breast Neoplasms / enzymology*
  • Breast Neoplasms / genetics*
  • Breast Neoplasms / pathology
  • Cannabinoids / pharmacology*
  • Cannabis
  • Cyclooxygenase 2 / metabolism*
  • Down-Regulation / drug effects*
  • Enzyme Inhibitors / pharmacology*
  • Female
  • Gene Expression / drug effects
  • Humans
  • Neoplasm Metastasis
  • Real-Time Polymerase Chain Reaction
  • Tumor Cells, Cultured
  • Up-Regulation / drug effects

Substances

  • Antineoplastic Agents, Phytogenic
  • BHLHE41 protein, human
  • Basic Helix-Loop-Helix Transcription Factors
  • Cannabinoids
  • Enzyme Inhibitors
  • Cyclooxygenase 2
  • PTGS2 protein, human
  • cannabidiolic acid