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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

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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.

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Acknowledgments

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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Authors and Affiliations

  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

    Shuso Takeda

  2. Department of Molecular Biology, Daiichi University of Pharmacy, 22-1 Tamagawa-cho, Minami-ku, Fukuoka, 815-8511, Japan

    Shuso Takeda, Taichi Himeno, Kazuhiro Kakizoe, Hiroyuki Okazaki & Hironori Aramaki

  3. Biomedical Research Institute, National Institute of Advanced Industrial Science and Technology (AIST), 1-1-1, Higashi, Tsukuba, Ibaraki, 305-8566, Japan

    Tomoko Okada

  4. Pharmaceutical Education Center, Daiichi University of Pharmacy, 22-1 Tamagawa-cho, Minami-ku, Fukuoka, 815-8511, Japan

    Kazuhito Watanabe

  5. Drug Innovation Research Center, Daiichi University of Pharmacy, 22-1 Tamagawa-cho, Minami-ku, Fukuoka, 815-8511, Japan

    Hironori Aramaki

Authors
  1. Shuso Takeda
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  2. Taichi Himeno
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  3. Kazuhiro Kakizoe
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  4. Hiroyuki Okazaki
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  5. Tomoko Okada
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  6. Kazuhito Watanabe
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  7. Hironori Aramaki
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Correspondence to Hironori Aramaki.

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Takeda, S., Himeno, T., Kakizoe, K. et al. 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 71, 286–291 (2017). https://doi.org/10.1007/s11418-016-1030-0

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  • DOI: https://doi.org/10.1007/s11418-016-1030-0

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