Journal of Natural Medicines

, Volume 71, Issue 1, pp 286–291 | Cite as

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

  • Shuso Takeda
  • Taichi Himeno
  • Kazuhiro Kakizoe
  • Hiroyuki Okazaki
  • Tomoko Okada
  • Kazuhito Watanabe
  • Hironori AramakiEmail author


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.


Cannabidiolic acid Cyclooxygenase-2 c-fos MDA-MB-231 cells Fiber-type cannabis plant 



This study was supported in part by a Grant-in-Aid for Scientific Research (C) (25460182 to S.T.) and in part by a Grant-in-Aid for Young Scientists (Start-up) (15K19167 to H.O.) from the Japan Society for the Promotion of Science (JSPS) KAKENHI.


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Copyright information

© The Japanese Society of Pharmacognosy and Springer Japan 2016

Authors and Affiliations

  • Shuso Takeda
    • 1
    • 2
  • Taichi Himeno
    • 2
  • Kazuhiro Kakizoe
    • 2
  • Hiroyuki Okazaki
    • 2
  • Tomoko Okada
    • 3
  • Kazuhito Watanabe
    • 4
  • Hironori Aramaki
    • 2
    • 5
    Email author
  1. 1.Laboratory of Xenobiotic Metabolism and Environmental Toxicology, Faculty of Pharmaceutical SciencesHiroshima International University (HIU)KureJapan
  2. 2.Department of Molecular BiologyDaiichi University of PharmacyFukuokaJapan
  3. 3.Biomedical Research InstituteNational Institute of Advanced Industrial Science and Technology (AIST)TsukubaJapan
  4. 4.Pharmaceutical Education CenterDaiichi University of PharmacyFukuokaJapan
  5. 5.Drug Innovation Research CenterDaiichi University of PharmacyFukuokaJapan

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