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

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.

Author information

1
Laboratory of Xenobiotic Metabolism and Environmental Toxicology, Faculty of Pharmaceutical Sciences, Hiroshima International University (HIU), 5-1-1 Hiro-koshingai, Kure, Hiroshima, 737-0112, Japan.
2
Department of Molecular Biology, Daiichi University of Pharmacy, 22-1 Tamagawa-cho, Minami-ku, Fukuoka, 815-8511, Japan.
3
Biomedical Research Institute, National Institute of Advanced Industrial Science and Technology (AIST), 1-1-1, Higashi, Tsukuba, Ibaraki, 305-8566, Japan.
4
Pharmaceutical Education Center, Daiichi University of Pharmacy, 22-1 Tamagawa-cho, Minami-ku, Fukuoka, 815-8511, Japan.
5
Department of Molecular Biology, Daiichi University of Pharmacy, 22-1 Tamagawa-cho, Minami-ku, Fukuoka, 815-8511, Japan. haramaki@daiichi-cps.ac.jp.
6
Drug Innovation Research Center, Daiichi University of Pharmacy, 22-1 Tamagawa-cho, Minami-ku, Fukuoka, 815-8511, Japan. haramaki@daiichi-cps.ac.jp.

Abstract

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

PMID:
27530354
DOI:
10.1007/s11418-016-1030-0
[Indexed for MEDLINE]

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