title: 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.
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.
authors.affiliation: 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.|Department of Molecular Biology, Daiichi University of Pharmacy, 22-1 Tamagawa-cho, Minami-ku, Fukuoka, 815-8511, Japan.
authors.forename: Shuso
authors.initials: S
authors.lastname: Takeda
authors.affiliation: Department of Molecular Biology, Daiichi University of Pharmacy, 22-1 Tamagawa-cho, Minami-ku, Fukuoka, 815-8511, Japan.
authors.forename: Taichi
authors.initials: T
authors.lastname: Himeno
authors.affiliation: Department of Molecular Biology, Daiichi University of Pharmacy, 22-1 Tamagawa-cho, Minami-ku, Fukuoka, 815-8511, Japan.
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Kakizoe
authors.affiliation: Department of Molecular Biology, Daiichi University of Pharmacy, 22-1 Tamagawa-cho, Minami-ku, Fukuoka, 815-8511, Japan.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Okazaki
authors.affiliation: Biomedical Research Institute, National Institute of Advanced Industrial Science and Technology (AIST), 1-1-1, Higashi, Tsukuba, Ibaraki, 305-8566, Japan.
authors.forename: Tomoko
authors.initials: T
authors.lastname: Okada
authors.affiliation: Pharmaceutical Education Center, Daiichi University of Pharmacy, 22-1 Tamagawa-cho, Minami-ku, Fukuoka, 815-8511, Japan.
authors.forename: Kazuhito
authors.initials: K
authors.lastname: Watanabe
authors.affiliation: Department of Molecular Biology, Daiichi University of Pharmacy, 22-1 Tamagawa-cho, Minami-ku, Fukuoka, 815-8511, Japan. haramaki@daiichi-cps.ac.jp.|Drug Innovation Research Center, Daiichi University of Pharmacy, 22-1 Tamagawa-cho, Minami-ku, Fukuoka, 815-8511, Japan. haramaki@daiichi-cps.ac.jp.
authors.forename: Hironori
authors.initials: H
authors.lastname: Aramaki
mesh_terms: D001943:Breast Neoplasms / Q000235:genetics*; D002186:Cannabinoids / Q000737:chemistry*; D018929:Cell Culture Techniques; D045744:Cell Line, Tumor; D002465:Cell Movement; D015536:Down-Regulation; D005260:Female; D006801:Humans; D009361:Neoplasm Invasiveness; D016760:Proto-Oncogene Proteins c-fos / Q000235:genetics*
chemical_list: D002186:Cannabinoids; D016760:Proto-Oncogene Proteins c-fos; C006884:cannabidiolic acid
keywords: Cannabidiolic acid; Cyclooxygenase-2; Fiber-type cannabis plant; MDA-MB-231 cells; c-fos