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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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.
KeywordsCannabidiolic 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.
- 8.Bolognini D, Rock EM, Cluny NL, Cascio MG, Limebeer CL, Duncan M, Stott CG, Javid FA, Parker LA, Pertwee RG (2013) Cannabidiolic acid prevents vomiting in Suncus murinus and nausea-induced behaviour in rats by enhancing 5-HT1A receptor activation. Br J Pharmacol 168:1456–1470CrossRefPubMedPubMedCentralGoogle Scholar
- 10.Takeda S, Okajima S, Miyoshi H, Yoshida K, Okamoto Y, Okada T, Amamoto T, Watanabe K, Omiecinski CJ, Aramaki H (2012) Cannabidiolic acid, a major cannabinoid in fiber-type cannabis, is an inhibitor of MDA-MB-231 breast cancer cell migration. Toxicol Lett 214:314–319CrossRefPubMedPubMedCentralGoogle Scholar
- 18.Takeda S, Yoshida K, Nishimura H, Harada M, Okajima S, Miyoshi H, Okamoto Y, Amamoto T, Watanabe K, Omiecinski CJ, Aramaki H (2013) Δ9-Tetrahydrocannabinol disrupts estrogen-signaling through up-regulation of estrogen receptor β (ERβ). Chem Res Toxicol 26:1073–1079CrossRefPubMedPubMedCentralGoogle Scholar
- 20.Takeda S, Ikeda E, Su S, Harada M, Okazaki H, Yoshioka Y, Nishimura H, Ishii H, Kakizoe K, Taniguchi A, Tokuyasu M, Himeno T, Watanabe K, Omiecinski CJ, Aramaki H (2014) ∆9-THC modulation of fatty acid 2-hydroxylase (FA2H) gene expression: possible involvement of induced levels of PPARα in MDA-MB-231 breast cancer cells. Toxicology 326:18–24CrossRefPubMedGoogle Scholar
- 24.Ford LA, Roelofs AJ, Anavi-Goffer S, Mowat L, Simpson DG, Irving AJ, Rogers MJ, Rajnicek AM, Ross RA (2010) A role for L-α-lysophosphatidylinositol and GPR55 in the modulation of migration, orientation and polarization of human breast cancer cells. Br J Pharmacol 160:762–771CrossRefPubMedPubMedCentralGoogle Scholar