The Korean Journal of Physiology and Pharmacology

The Korean Society of Pharmacology (대한약리학회)
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MDL-12330A potentiates TRAIL-induced apoptosis in gastric cancer cells through CHOP-mediated DR5 upregulation

  • Lim, Sung-Chul (Department of Pathology, College of Medicine, Chosun University) ;
  • Han, Song Iy (Division of Premedical Science, College of Medicine, Chosun University)
  • Received : 2017.02.08
  • Accepted : 2017.04.04
  • Published : 2017.07.01
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Abstract

MDL-12330A is a widely used adenylyl cyclase (AC) inhibitor that blocks AC/cAMP signaling. In this study, we demonstrated a novel antitumor activity of this drug in gastric carcinoma (GC) cell lines. In these GC cells, MDL-12330A reduced cell viability and induced cell death in a concentration-dependent manner. At a moderate concentration (${\sim}20{\mu}M$), MDL-12330A mainly induced apoptotic death whereas at concentrations greater than $20{\mu}M$, it increased non-apoptotic cell death. The induction of apoptosis was at least partially regulated by CHOP-mediated DR5 upregulation, as detected by immunoblotting and gene interference assays. More importantly, low concentrations of MDL-12330A effectively enhanced recombinant human tumor necrosis factor (TNF)-related apoptosis-inducing ligand (rhTRAIL)-induced apoptosis and clonogenicity in these gastric cancer cells. This study demonstrates a possible role of MDL-12330A as a potential sensitizer to TRAIL, and suggests a novel therapeutic strategy targeting gastric cancer cells.

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References

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