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

Noh,Eun-Mi; Chung,Eun  Yong; Youn,Hyun  Jo; Jung,Sung  Hoo; Hur,Hyun; Lee,Young-Rae; Kim,Jong-Suk

doi:10.3892/ijmm.2012.1214

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

Authors:
- Eun-Mi Noh
- Eun Yong Chung
- Hyun Jo Youn
- Sung Hoo Jung
- Hyun Hur
- Young-Rae Lee
- Jong-Suk Kim
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Affiliations: Department of Biochemistry and Institute for Medical Sciences, Chonbuk National University Medical School, Jeonju 560‑182, Republic of Korea, Department of Anesthesiology and Pain Medicine, Bucheon St. Mary's Hospital, Catholic University of Korea, Bucheon 420-717, Republic of Korea, Department of Surgery, Division of Breast-Thyroid Surgery, Chonbuk National University Medical School, Jeonju 560-182, Republic of Korea, Department of Oral Biochemistry, School of Dentistry, Wonkwang University, Iksan 570-749, Republic of Korea
Published online on: December 14, 2012 https://doi.org/10.3892/ijmm.2012.1214
Pages: 393-399

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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.

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