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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.
AuthorsEun-Mi Noh, Eun Yong Chung, Hyun Jo Youn, Sung Hoo Jung, Hyun Hur, Young-Rae Lee, Jong-Suk Kim
JournalInternational journal of molecular medicine (Int J Mol Med) Vol. 31 Issue 2 Pg. 393-9 (Feb 2013) ISSN: 1791-244X [Electronic] Greece
PMID23242121 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Antineoplastic Agents, Phytogenic
  • NF-kappa B
  • Pregnenediones
  • Transcription Factor AP-1
  • pregna-4,17-diene-3,16-dione
  • I-kappa B Kinase
  • Mitogen-Activated Protein Kinases
  • Matrix Metalloproteinase 9
  • Tetradecanoylphorbol Acetate
Topics
  • Antineoplastic Agents, Phytogenic (chemistry, pharmacology)
  • Breast (drug effects, metabolism, pathology)
  • Breast Neoplasms (drug therapy, metabolism, pathology)
  • Cell Survival (drug effects)
  • Commiphora (chemistry)
  • Female
  • Humans
  • I-kappa B Kinase (antagonists & inhibitors, metabolism)
  • Isomerism
  • MCF-7 Cells
  • Matrix Metalloproteinase 9 (genetics)
  • Mitogen-Activated Protein Kinases (antagonists & inhibitors, metabolism)
  • NF-kappa B (antagonists & inhibitors, metabolism)
  • Neoplasm Invasiveness (prevention & control)
  • Pregnenediones (chemistry, pharmacology)
  • Signal Transduction (drug effects)
  • Tetradecanoylphorbol Acetate (pharmacology)
  • Transcription Factor AP-1 (antagonists & inhibitors, metabolism)

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