P-227 - Cordycepin inhibits lipopolysaccharide-induced cell migration and invasion in human colorectal carcinoma HCT116 cells through down-regulation of pro...

Date 04 July 2015
Event WorldGI 2015
Session Posters
Topics Cancer Biology
Colon and Rectal Cancer
Basic Scientific Principles
Presenter Y.H. Choi
Citation Annals of Oncology (2015) 26 (suppl_4): 1-100. 10.1093/annonc/mdv233
Authors Y.H. Choi1, C. Park2, Y.H. Yoo3, M.H. Han4, J.-. Jeong4
  • 1Dongeui University, Busan/KR
  • 2Dongeui University College of Natural Sciences and Human Ecology, Busan/KR
  • 3Dong-A University College of Medicine and Mitochondria Hub Regulation Center, Busan/KR
  • 4Dongeui University College of Korean Medicine, Busan/KR

Abstract

Introduction

Prostaglandin E2 (PGE2), a major product of cyclooxygenase-2 (COX-2), plays an important role in 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 is growing interest in the therapeutic potential of targeting EPs. In the present study, we investigated the roles of EP4 on effectiveness of cordycepin in inhibiting migration and invasion of HCT116 human colorectal carcinoma cells.

Methods

We employed invasion, migration and gelatin zymography assays to characterize the effect of cordycepin in lipopolysaccharide (LPS)-stimulated HCT116 cells. Transient transfection, reverse transcription-PCR, immunoblotting and small interfering RNA (siRNA)-mediated knockdown analyses were performed to investigate gene promoter activities and underlying mechanisms, respectively.

Results

Our data indicated that cordycepin suppressed LPS-enhanced cell migration and invasion through inactivation of MMP-9, and down-regulation of COX-2 expression and PGE2 production. The events were associated with inactivation of EP4 and activation of AMP-activated protein kinase (AMPK). Moreover, AH23848, an EP4 antagonist, prevented LPS-induced MMP-9 expression and cell invasion in HCT116 cells. However, an AMPK inhibitor, compound C, and knockdown of AMPK activity by siRNA attenuated the cordycepin-induced inhibition of EP4 expression. Cordycepin treatment also reduced the transcriptional activity of cAMP responsive element-binding protein (CREB).

Conclusion

These findings provide evidence that cordycepin suppresses the migration and invasion of HCT116 cells through modulating EP4 expression and AMPK-CREB signaling pathway. Therefore, cordycepin has the potential to be a potent anticancer agent for designing therapeutic strategies against colorectal cancer metastasis. [This research was supported by Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Science, ICT & Future Planning (2014R1A1A1008460 & & 2012046358)]