title: Orostachys japonicus inhibits the expression of MMP-2 and MMP-9 mRNA and modulates the expression of iNOS and COX-2 genes in human PMA-differentiated THP-1 cells via inhibition of NF-κB and MAPK activation.
abstract: Orostachys japonicus has been used in traditional medicine as an anticancer agent. The present study aimed to investigate the mechanism by which O. japonicus extract affects the expression of matrix metalloproteinase (MMP)-2 and MMP-9, its association with the expression of the inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) genes in phorbol myristate acetate-differentiated THP-1 human monocytic leukemia cells and how it mediates the nuclear factor (NF)-κB and mitogen-activated protein kinase (MAPK) pathways. Cell proliferation was analyzed by MTT assay, mRNA expression was detected by quantitative polymerase chain reaction and protein expression was measured by western blot analysis. It was demonstrated that O. japonicus suppressed the mRNA expression of MMP-2 and MMP-9. In addition, O. japonicus was found to downregulate iNOS and COX-2 transcription and translocation. Furthermore, O. japonicus inhibited NF-κB p65 activity as well as the phosphorylation of p38 MAPK, MAPK kinase (MEK) and extracellular signal regulated kinase (ERK). The present results suggested that O. japonicus inhibited not only MMP-2 and MMP-9 mRNA expression, but also iNOS and COX-2 gene expression, suppressed NF-κB activation and reduced phosphorylation of p38 MAPK, MEK and ERK. The present results therefore indicated that O. japonicus was able to inhibit the expression of MMP-2 and MMP-9 and suppress the transcription and translocation of iNOS and COX-2 by directly inhibiting the activation of NF-κB and the phosphorylation of the MAPK pathway in THP-1 cells.
authors.affiliation: Medical Science Research Institute, Kyung Hee University Medical Center, Seoul 130‑872, Republic of Korea.
authors.forename: Young Il
authors.initials: YI
authors.lastname: Kim
authors.affiliation: Department of Biotechnology, Catholic University of Daegu, Daegu 712‑702, Republic of Korea.
authors.forename: Seung-Won
authors.initials: SW
authors.lastname: Park
authors.affiliation: Department of Internal Medicine, College of Korean Medicine, Kyung Hee University, Seoul 130‑872, Republic of Korea.
authors.forename: Yeo-Kwang
authors.initials: YK
authors.lastname: Yoon
authors.affiliation: Department of Internal Medicine, College of Korean Medicine, Kyung Hee University, Seoul 130‑872, Republic of Korea.
authors.forename: Kyung-Wook
authors.initials: KW
authors.lastname: Lee
authors.affiliation: Department of Internal Medicine, College of Korean Medicine, Kyung Hee University, Seoul 130‑872, Republic of Korea.
authors.forename: Jang-Hoon
authors.initials: JH
authors.lastname: Lee
authors.affiliation: Department of Internal Medicine, College of Korean Medicine, Kyung Hee University, Seoul 130‑872, Republic of Korea.
authors.forename: Hong-Jung
authors.initials: HJ
authors.lastname: Woo
authors.affiliation: Department of Internal Medicine, College of Korean Medicine, Kyung Hee University, Seoul 130‑872, Republic of Korea.
authors.forename: Youngchul
authors.initials: Y
authors.lastname: Kim
mesh_terms: D002454:Cell Differentiation / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D029627:Crassulaceae / Q000737:chemistry; D051546:Cyclooxygenase 2 / Q000096:biosynthesis* / Q000235:genetics; D015973:Gene Expression Regulation, Leukemic; D006801:Humans; D007938:Leukemia / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D020935:MAP Kinase Signaling System; D020778:Matrix Metalloproteinase 2 / Q000096:biosynthesis* / Q000235:genetics; D020780:Matrix Metalloproteinase 9 / Q000096:biosynthesis* / Q000235:genetics; D016328:NF-kappa B / Q000096:biosynthesis / Q000235:genetics; D052247:Nitric Oxide Synthase Type II / Q000096:biosynthesis* / Q000235:genetics; D010766:Phosphorylation / Q000187:drug effects; D010936:Plant Extracts / Q000008:administration & dosage / Q000737:chemistry; D012333:RNA, Messenger / Q000096:biosynthesis; D013755:Tetradecanoylphorbol Acetate / Q000008:administration & dosage
chemical_list: D016328:NF-kappa B; D010936:Plant Extracts; D012333:RNA, Messenger; C496319:NOS2 protein, human; D052247:Nitric Oxide Synthase Type II; D051546:Cyclooxygenase 2; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9; D013755:Tetradecanoylphorbol Acetate