Biomolecules & Therapeutics
Thymoquinone Suppresses Migration of Human Renal Carcinoma Caki-1 Cells through Inhibition of the PGE2-Mediated Activation of the EP2 Receptor Pathway
Geumi Park1,†, Na-Young Song2,†, Do-Hee Kim3,†, Su-Jun Lee4 and Kyung-Soo Chun1,*
1College of Pharmacy, Keimyung University, Daegu 42601,
2College of Dentistry, Younsei University, Seoul 03722,
3Department of Chemistry, College of Convergence and Integrated Science, Kyonggi University, Suwon 16227,
4Department of Pharmacology and Pharmacogenomics Research Center, Inje University College of Medicine, Busan 47392, Republic of Korea
Tel: +82-53-580-6647, Fax: +82-53-580-6645
The first three authors contributed equally to this work.
Received: March 31, 2020; Revised: June 7, 2020; Accepted: July 16, 2020; Published online: August 26, 2020.
© The Korean Society of Applied Pharmacology. All rights reserved.

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License ( by-nc/4.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
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.
Keywords: Thymoquinone, Renal cell carcinoma (RCC), Prostaglandin E2 (PGE2), EP2 receptor, MMP-9

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