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Thymoquinone Suppresses Migration of Human Renal Carcinoma Caki-1 Cells through Inhibition of the PGE2-Mediated Activation of the EP2 Receptor Pathway

Authors
 Geumi Park  ;  Na-Young Song  ;  Do-Hee Kim  ;  Su-Jun Lee  ;  Kyung-Soo Chun 
Citation
 BIOMOLECULES & THERAPEUTICS, Vol.29(1) : 64-72, 2021-01 
Journal Title
 BIOMOLECULES & THERAPEUTICS 
ISSN
 1976-9148 
Issue Date
2021-01
Keywords
EP2 receptor ; MMP-9 ; Prostaglandin E2 (PGE2) ; Renal cell carcinoma (RCC) ; Thymoquinone
Abstract
Renal cell carcinoma (RCC) is likely to metastasize to other organs, and is often resistant to conventional chemotherapies. Thymoquinone (TQ), a phytochemical derived from the seeds of Nigella sativa, has been shown to inhibit migration and metastasis in various cancers. In this study, we assessed the effect of TQ on the migratory activity of human RCC Caki-1 cells. We found that treatment with TQ reduced the proteolytic activity of matrix metalloproteinase-9 (MMP-9) in Caki-1 cells. TQ significantly repressed prostaglandin E2 (PGE2) production, its EP2 receptor expression as well as the activation of Akt and p38, the wellknown upstream signal proteins of MMP-9. In addition, treatment with butaprost, a PGE2 agonist, also induced MMP-9 activity and migration/invasion in Caki-1 cells. Moreover, pharmacological inhibitors of PI3K/Akt and p38 remarkably attenuated butaprostinduced Caki-1 cell migration and invasion, implying that activation of PI3K/Akt and p38 is a bridge between the PGE2-EP2 axis and MMP-9-dependent migration and invasion. Taken together, these data suggest that TQ is a promising anti-metastatic drug to treat advanced and metastatic RCC.
DOI
10.4062/biomolther.2020.048
Appears in Collections:
2. College of Dentistry (치과대학) > Dept. of Oral Biology (구강생물학교실) > 1. Journal Papers
Yonsei Authors
Song, Na-Young(송나영) ORCID logo https://orcid.org/0000-0001-8658-7049
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/182010
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