- Hironori Aramaki (Department of Molecular Biology, Daiichi University of Pharmacy / Drug Innovation Research Center, Daiichi University of Pharmacy / email@example.com)
1) Department of Molecular Biology, Daiichi University of Pharmacy , 2) Laboratory of Xenobiotic Metabolism and Environmental Toxicology, Faculty of Pharmaceutical Sciences, Hiroshima International University (HIU) , 3) Drug Innovation Research Center, Daiichi University of Pharmacy , 4) Biomedical Research Institute, National Institute of Advanced Industrial Science and Technology (AIST)
We previously identified cannabidiolic acid (CBDA), a major component of the fibertype cannabis plant, as an inhibitor of MDA-MB-231 human breast cancer cell migration in vitro (Takeda et al., 2012). Although MDA-MB-231 is a widely used human breast cancer cell line in in vitro and in vivo studies, these cells have to be injected into nude mice (immunodeficient animals) in in vivo trials. Thus, we established the murine breast cancer cell line, 4T1E/M3, which is highly metastatic to bone in BALB/c mice (Takahashi et al., 2008, 2009; Sakai et al., 2012); this murine syngeneic tumor model may be useful for identifying molecular targets for therapeutic interventions. Prior to in vivo experiments using the murine tumor model, we herein performed DNA microarray analyses of 4T1E/M3 cells, treated with CBDA for 48 hr at a sub-toxic concentration (25 μM), in order to comprehensively analyze the effects of CBDA on the genes involved in the bone metastasis of breast cancers. The results obtained revealed that the expression of matrix metalloproteinase-9 (MMP-9), transforming growth factor-β (TGF-β) inducible gene H3 (BIGH3), and parathyroid hormone-related protein (PTHrP) was markedly down-regulated by 0.11-fold, 0.22-fold, and 0.15-fold, respectively; these molecules were mutually involved in the bone metastasis of breast cancer cells.