BMB Reports 2018; 51(10): 532-537
Cordycepin inhibits lipopolysaccharide-induced cell migration and invasion in human colorectal carcinoma HCT-116 cells through down-regulation of prostaglandin E2 receptor EP4
Jin-Woo Jeong1, Cheol Park2, Hee-Jae Cha3, Su Hyun Hong4,5, Shin-Hyung Park6, Gi-Young Kim7, Woo Jean Kim8, Cheol Hong Kim9, Kyoung Seob Song10,* and Yung Hyun Choi4,5,*
1Freshwater Bioresources Utilization Bureau, Nakdonggang National Institute of Biological Resources, Sangju 17104, 2Department of Molecular Biology, College of Natural Sciences, Dongeui University, Busan 47340, 3Department of Parasitology and Genetics, Kosin University College of Medicine, Busan 49267, 4Department of Biochemistry, Dong-Eui University College of Korean Medicine, Busan 47227, 5Anti-Aging Research Center, Dong-Eui University, Busan 47340, 6Department of Pathology, Dong-Eui University College of Korean Medicine, Busan 47227, 7Department of Marine Life Sciences, Jeju National University, Jeju 63243, 8Department of Anatomy, Kosin University College of Medicine, Busan 49267, 9Department of Pediatrics, Sungkyunkwan University Samsung Changwon Hospital, Changwon 51353, 10Department of Physiology, Kosin University College of Medicine, Busan 49267, Korea
Correspondence to:

Kyoung Seob Song, Tel: +82-51-990-6236; Fax: +82-51-990-3081; E-mail:;
Yung Hyun Choi, Tel: +82-51-850-7413; Fax: +82-51-853-4036; E-mail:

Received: May 28, 2018; Revised: June 29, 2018; Accepted: September 3, 2018; Published online: October 31, 2018.
© Korean Society for Biochemistry and Molecular Biology. All rights reserved.

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Prostaglandin E2 (PGE2), a major product of cyclooxygenase-2 (COX-2), plays an important role in the carcinogenesis of many solid tumors, including colorectal cancer. Because PGE2 functions by signaling through PGE2 receptors (EPs), which regulate tumor cell growth, invasion, and migration, there has been a growing amount of interest in the therapeutic potential of targeting EPs. In the present study, we investigated the role of EP4 on the effectiveness of cordycepin in inhibiting the migration and invasion of HCT116 human colorectal carcinoma cells. Our data indicate that cordycepin suppressed lipopolysaccharide (LPS)-enhanced cell migration and invasion through the inactivation of matrix metalloproteinase (MMP)-9 as well as the down-regulation of COX-2 expression and PGE2 production. These events were shown to be associated with the inactivation of EP4 and activation of AMP-activated protein kinase (AMPK). Moreover, the EP4 antagonist AH23848 prevented LPS-induced MMP-9 expression and cell invasion in HCT116 cells. However, the AMPK inhibitor, compound C, as well as AMPK knockdown via siRNA, attenuated the cordycepin-induced inhibition of EP4 expression. Cordycepin treatment also reduced the activation of CREB. These findings indicate that cordycepin suppresses the migration and invasion of HCT116 cells through modulating EP4 expression and the AMPK-CREB signaling pathway. Therefore, cordycepin has the potential to serve as a potent anti-cancer agent in therapeutic strategies against colorectal cancer metastasis.
Keywords: AMPK, Cell migration/invasion, Cordycepin, CREB, EP4

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Funding Information
  • National Research Foundation of Korea(NRF)
      NRF-2016R1C1B1014724, 2016R1D1A1B03932521, 2018R1A2B2005705


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