title: Cis-guggulsterone inhibits the IKK/NF-κB pathway, whereas trans-guggulsterone inhibits MAPK/AP-1 in MCF‑7 breast cancer cells: guggulsterone regulates MMP‑9 expression in an isomer-specific manner.
abstract: Νuclear factor-κB (NF-κB) and activator protein-1 (AP-1) are major transcription             factors that have been associated with breast cancer metastasis by inducing matrix             metalloproteinase-9 (MMP-9) expression. In this study, we investigated the inhibitory             effects of guggulsterone isomers (cis or trans) on 12-O-tetradecanoylpho-bol-13-acetate             (TPA)-induced MMP-9 expression. Cis-guggulsterone inhibited TPA-induced MMP expression             by blocking IκB kinase (IKK)/NF-κB signaling, whereas trans-guggulsterone blocked             mitogen-activated protein kinase (MAPK)/AP-1 signaling. Cis-guggulsterone was             more potent than trans-guggulsterone in the inhibition of TPA-induced MMP-9 expression             and invasion of MCF-7 cells. Furthermore, we found that the combination of these             isomers exerted an additive effect on the inhibition of MCF-7 cell invasion. These             results suggest that guggulsterone isomers downregulate MMP-9 expression and tumor             cell invasion through the isomer-specific suppression of IKK/NF-κB and MAPK/AP-1             activation. In addition, the suppression of MMP-9 expression correlated well with             the inhibition of cell invasion.
authors.affiliation: Department of Biochemistry and Institute for Medical Sciences,                     Chonbuk National University Medical School, Jeonju 560‑182, Republic of                     Korea.
authors.forename: Eun-Mi
authors.initials: EM
authors.lastname: Noh
authors.forename: Eun Yong
authors.initials: EY
authors.lastname: Chung
authors.forename: Hyun Jo
authors.initials: HJ
authors.lastname: Youn
authors.forename: Sung Hoo
authors.initials: SH
authors.lastname: Jung
authors.forename: Hyun
authors.initials: H
authors.lastname: Hur
authors.forename: Young-Rae
authors.initials: YR
authors.lastname: Lee
authors.forename: Jong-Suk
authors.initials: JS
authors.lastname: Kim
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000737:chemistry / Q000494:pharmacology*; D001940:Breast / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D002470:Cell Survival / Q000187:drug effects; D029744:Commiphora / Q000737:chemistry; D005260:Female; D006801:Humans; D051550:I-kappa B Kinase / Q000037:antagonists & inhibitors / Q000378:metabolism*; D007536:Isomerism; D061986:MCF-7 Cells; D020780:Matrix Metalloproteinase 9 / Q000235:genetics*; D020928:Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000378:metabolism*; D009361:Neoplasm Invasiveness / Q000517:prevention & control; D011282:Pregnenediones / Q000737:chemistry / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D018808:Transcription Factor AP-1 / Q000037:antagonists & inhibitors / Q000378:metabolism*
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D016328:NF-kappa B; D011282:Pregnenediones; D018808:Transcription Factor AP-1; C023617:pregna-4,17-diene-3,16-dione; D051550:I-kappa B Kinase; D020928:Mitogen-Activated Protein Kinases; D020780:Matrix Metalloproteinase 9; D013755:Tetradecanoylphorbol Acetate