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http://dx.doi.org/10.5483/BMBRep.2020.53.4.164

15d-PGJ2 inhibits NF-κB and AP-1-mediated MMP-9 expression and invasion of breast cancer cell by means of a heme oxygenase-1-dependent mechanism  

Jang, Hye-Yeon (Department of Biochemistry, Institute for Medical Sciences, Chonbuk National University Medical School)
Hong, On-Yu (Department of Biochemistry, Institute for Medical Sciences, Chonbuk National University Medical School)
Youn, Hyun Jo (Department of Surgery, Research Institute of Clinical Medicine, Chonbuk National University Hospital, Chonbuk National University and Biomedical Research Institute)
Kim, Min-Gul (Department of Pharmacology, Institute for Medical Sciences, Chonbuk National University Medical School)
Kim, Cheorl-Ho (Molecular and Cellular Glycobiology Unit, Department of Biological Sciences, Sung Kyun Kwan University)
Jung, Sung Hoo (Department of Surgery, Research Institute of Clinical Medicine, Chonbuk National University Hospital, Chonbuk National University and Biomedical Research Institute)
Kim, Jong-Suk (Department of Biochemistry, Institute for Medical Sciences, Chonbuk National University Medical School)
Publication Information
BMB Reports / v.53, no.4, 2020 , pp. 212-217 More about this Journal
Abstract
Activation of peroxisome proliferator-activated receptor γ (PPARγ) serves as a key factor in the proliferation and invasion of breast cancer cells and is a potential therapeutic target for breast cancer. However, the mechanisms underlying this effect remain largely unknown. Heme oxygenase-1 (HO-1) is induced and over-expressed in various cancers and is associated with features of tumor aggressiveness. Recent studies have shown that HO-1 is a major downstream target of PPARγ. In this study, we investigated the effects of induction of HO-1 by PPARγ on TPA-induced MMP-9 expression and cell invasion using MCF-7 breast cancer cells. TPA treatment increased NF-κB /AP-1 DNA binding as well as MMP-9 expression. These effects were significantly blocked by 15d-PGJ2, a natural PPARγ ligand. 15d-PGJ2 induced HO-1 expression in a dose-dependent manner. Interestingly, HO-1 siRNA significantly attenuated the inhibition of TPA-induced MMP-9 protein expression and cell invasion by 15d-PGJ2. These results suggest that 15d-PGJ2 inhibits TPA-induced MMP-9 expression and invasion of MCF-7 cells by means of a heme oxygenase-1-dependent mechanism. Therefore, PPARγ/HO-1 signaling-pathway inhibition may be beneficial for prevention and treatment of breast cancer.
Keywords
Heme oxygenase-1; MCF-7; MMP-9; $PPAR{\gamma}$; $15d-PGJ_2$;
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