Biomol Ther.  2021 Jan;29(1):64-72. 10.4062/biomolther.2020.048.

Thymoquinone Suppresses Migration of Human Renal Carcinoma Caki-1 Cells through Inhibition of the PGE 2 -Mediated Activation of the EP2 Receptor Pathway

  • 1College of Pharmacy, Keimyung University, Daegu 42601, Republic of Korea
  • 2College of Dentistry, Younsei University, Seoul 03722, Republic of Korea
  • 3Department of Chemistry, College of Convergence and Integrated Science, Kyonggi University, Suwon 16227, Republic of Korea
  • 4Department of Pharmacology and Pharmacogenomics Research Center, Inje University College of Medicine, Busan 47392, Republic of Korea


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.


Thymoquinone; Renal cell carcinoma (RCC); Prostaglandin E 2 (PGE2); EP2 receptor; MMP-9
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