Cannabidiolic acid-mediated selective down-regulation of c-fos in highly aggressive breast cancer MDA-MB-231 cells: possible involvement of its down-regulation in the abrogation of aggressiveness

J Nat Med. 2017 Jan;71(1):286-291. doi: 10.1007/s11418-016-1030-0. Epub 2016 Aug 16.


The physiological activities of cannabidiolic acid (CBDA), a component of fiber-type cannabis plants, have been demonstrated and include its function as a protector against external invasion by inducing cannabinoid-mediated necrosis (Shoyama et al., Plant Signal Behav 3:1111-1112, 2008). The biological activities of CBDA have been attracting increasing attention. We previously identified CBDA as an inhibitor of the migration of MDA-MB-231 cells, a widely used human breast cancer cell line in cancer biology, due to its highly aggressive nature. The chemical inhibition and down-regulation of cyclooxygenase-2 (COX-2), the expression of which has been detected in ~40 % of human invasive breast cancers, are suggested to be involved in the CBDA-mediated abrogation of cell migration. However, the molecular mechanism(s) responsible for the CBDA-induced down-regulation of COX-2 in MDA-MB-231 cells have not yet been elucidated. In the present study, we describe a possible mechanism by which CBDA abrogates the expression of COX-2 via the selective down-regulation of c-fos, one component of the activator protein-1 (AP-1) dimer complex, a transcription factor for the positive regulation of the COX-2 gene.

Keywords: Cannabidiolic acid; Cyclooxygenase-2; Fiber-type cannabis plant; MDA-MB-231 cells; c-fos.

MeSH terms

  • Breast Neoplasms / genetics*
  • Cannabinoids / chemistry*
  • Cell Culture Techniques
  • Cell Line, Tumor
  • Cell Movement
  • Down-Regulation
  • Female
  • Humans
  • Neoplasm Invasiveness
  • Proto-Oncogene Proteins c-fos / genetics*


  • Cannabinoids
  • Proto-Oncogene Proteins c-fos
  • cannabidiolic acid