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.
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