title: The cadin-2-en-1β-ol-1β-D-glucuronopyranoside suppresses TPA-mediated matrix metalloproteinase-9 expression through the ERK signaling pathway in MCF-7 human breast adenocarcinoma cells.
abstract: A sesquiterpene glycoside, cadin-2-en-1β-ol-1β-D-glucuronopyranoside (known as CR4-1), was isolated from Catharanthus roseus (Apocynaceae) hairy root cultures. C. roseus is widely used as an ornamental and medicinal plant and is cultivated mainly for its alkaloids. C. roseus has been reported to have pharmacologic properties such as anti-cancer, enzymatic anti-oxidant, and anti-diabetic effects. In this study, we demonstrated that CR4-1 significantly inhibited the in vitro invasion of MCF-7 human breast adenocarcinoma cells induced by 12-O-tetradecanoyl phorbol-13-acetate (TPA). Matrix metalloproteinases (MMPs) are known to be involved in cancer invasion and metastasis. Zymographic analysis showed that CR4-1 suppressed TPA-induced MMP-9 activity in a dose-dependent manner. We further demonstrated that CR4-1 suppressed the phosphorylation of extracellular signal-regulated protein kinase, but not p38 kinase or c-Jun N-terminal kinase (JNK). Moreover, CR4-1 attenuated TPA-induced degradation of κBα inhibitor (IκB-α). These results suggest that CR4-1 reduces the invasiveness of human cancer cells by suppressing MMP-9 expression through inhibition of the NF-κB signaling pathways.
authors.affiliation: Department of Bioscience and Biotechnology, Bio/Molecular Informatics Center, Konkuk University, South Korea.
authors.forename: Jung-Hee
authors.initials: JH
authors.lastname: Kim
authors.forename: Man Sub
authors.initials: MS
authors.lastname: Kim
authors.forename: Yesol
authors.initials: Y
authors.lastname: Bak
authors.forename: Ill-Min
authors.initials: IM
authors.lastname: Chung
authors.forename: Do-Young
authors.initials: DY
authors.lastname: Yoon
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy* / Q000473:pathology; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage / Q000302:isolation & purification / Q000494:pharmacology; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology; D030008:Catharanthus / Q000737:chemistry*; D045744:Cell Line, Tumor; D004305:Dose-Response Relationship, Drug; D005260:Female; D005960:Glucosides / Q000008:administration & dosage / Q000302:isolation & purification / Q000494:pharmacology*; D006801:Humans; D020780:Matrix Metalloproteinase 9 / Q000235:genetics; D016328:NF-kappa B / Q000037:antagonists & inhibitors; D009361:Neoplasm Invasiveness; D010766:Phosphorylation / Q000187:drug effects; D012717:Sesquiterpenes / Q000008:administration & dosage / Q000302:isolation & purification / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D005960:Glucosides; D016328:NF-kappa B; D012717:Sesquiterpenes; C572717:cadin-2-en-1-ol-1-glucuronopyranoside; D020780:Matrix Metalloproteinase 9; D013755:Tetradecanoylphorbol Acetate