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15d-PGJ inhibits NF-リB and AP-1-mediated MMP-9 expression and invasion of breast cancer cell through a heme oxygenase-1-dependent mechanism.
Hye-Yeon Jang1,#, On-Yu Hong1, Hyun Jo Youn2, Min-Gul Kim3, Cheorl-Ho Kim4, Sung Hoo Jung2, Jong-Suk Kim1,*
1Department of Biochemistry, Institute for Medical Sciences, Chonbuk National University Medical School, Jeonju 54907, Republic of Korea,
2Department of Surgery, Research Institute of Clinical Medicine, Chonbuk National University Hospital, Chonbuk National University and Biomedical Research Institute, Jeonju 54907, Republic of Korea,
3Department of Pharmacology, Institute for Medical Sciences, Chonbuk National University Medical School, Jeonju, 54907, Republic of Korea,
4Molecular and Cellular Glycobiology Unit, Department of Biological Sciences, SungKyunKwan University, 300 Chunchun-Dong, Jangan-Gu, Suwon City, Kyunggi-Do 440-746, Korea
Abstract
Activation of peroxisome proliferator-activated receptor ャ (PPARャ) 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 PPARャ. In this study, we investigated the effects of induction of HO-1 by PPARャ on 12-O-tetradecanoylphorbol-13-acetate (TPA)–induced matrix metalloproteinase-9 (MMP-9) expression and cell invasion using MCF-7 breast cancer cells. TPA treatment increased NF-リB /AP-1 DNA binding as well as MMP-9 expression. These effects were significantly blocked by 15d-PGJ, a natural PPARャ ligand. 15d-PGJ 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-PGJ. These results suggest that 15d-PGJ inhibits TPA-induced MMP-9 expression and invasion of MCF-7 cells through a heme oxygenase-1-dependent mechanism. Therefore, PPARャ/HO-1 signaling pathway inhibition may be beneficial for prevention and treatment of breast cancer.
Abstract, Accepted Manuscript(in press) [Submitted on June 17, 2019, Accepted on September 24, 2019]
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