Thymoquinone suppresses migration of human renal carcinoma caki-1 cells through inhibition of the pge2-mediated activation of the ep2 receptor pathway

Geumi Park, Na Young Song, Do Hee Kim, Su Jun Lee, Kyung Soo Chun

Research output: Contribution to journalArticlepeer-review

4 Citations (Scopus)

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 well-known 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.

Original languageEnglish
Pages (from-to)64-72
Number of pages9
JournalBiomolecules and Therapeutics
Volume29
Issue number1
DOIs
Publication statusPublished - 2021

Bibliographical note

Funding Information:
This research was supported by the Basic Research Grant of Keimyung University in 2019.

Publisher Copyright:
© 2021 The Korean Society of Applied Pharmacology.

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Medicine
  • Pharmacology
  • Drug Discovery

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