title: Down-regulation of cyclooxygenase-2 (COX-2) by cannabidiolic acid in human breast cancer cells.
abstract: Metastases are known to be responsible for approximately 90% of breast cancer-related deaths. Cyclooxygenase-2 (COX-2) is involved not only in inflammatory processes, but also in the metastasis of cancer cells; it is expressed in 40% of human invasive breast cancers. To comprehensively analyze the effects of cannabidiolic acid (CBDA), a selective COX-2 inhibitor found in the fiber-type cannabis plant (Takeda et al., 2008), on COX-2 expression and the genes involved in metastasis, we performed a DNA microarray analysis of human breast cancer MDA-MB-231 cells, which are invasive breast cancer cells that express high levels of COX-2, treated with CBDA for 48 hr at 25 µM. The results obtained revealed that COX-2 and Id-1, a positive regulator of breast cancer metastasis, were down-regulated (0.19-fold and 0.52-fold, respectively), while SHARP1 (or BHLHE41), a suppressor of breast cancer metastasis, was up-regulated (1.72-fold) and CHIP (or STUB1) was unaffected (1.03-fold). These changes were confirmed by real-time RT-PCR analyses. Taken together, the results obtained here demonstrated that i) CBDA had dual inhibitory effects on COX-2 through down-regulation and enzyme inhibition, and ii) CBDA may possess the ability to suppress genes that are positively involved in the metastasis of cancer cells in vitro.
authors.affiliation: Department of Molecular Biology, Daiichi University of Pharmacy.
authors.forename: Shuso
authors.initials: S
authors.lastname: Takeda
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Okazaki
authors.forename: Eriko
authors.initials: E
authors.lastname: Ikeda
authors.forename: Satomi
authors.initials: S
authors.lastname: Abe
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Yoshioka
authors.forename: Kazuhito
authors.initials: K
authors.lastname: Watanabe
authors.forename: Hironori
authors.initials: H
authors.lastname: Aramaki
mesh_terms: D000972:Antineoplastic Agents, Phytogenic; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics; D001943:Breast Neoplasms / Q000201:enzymology* / Q000235:genetics* / Q000473:pathology; D002186:Cannabinoids / Q000494:pharmacology*; D002188:Cannabis; D051546:Cyclooxygenase 2 / Q000378:metabolism*; D015536:Down-Regulation / Q000187:drug effects*; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005260:Female; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D009362:Neoplasm Metastasis; D060888:Real-Time Polymerase Chain Reaction; D014407:Tumor Cells, Cultured; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D051792:Basic Helix-Loop-Helix Proteins; D002186:Cannabinoids; D051546:Cyclooxygenase 2; D004791:Enzyme Inhibitors; C422085:BHLHE41 protein, human; C496540:PTGS2 protein, human; C006884:cannabidiolic acid