MDL-12330A potentiates TRAIL-induced apoptosis in gastric cancer cells through CHOP-mediated DR5 upregulation.
10.4196/kjpp.2017.21.4.397
- Author:
Sung Chul LIM
1
;
Song Iy HAN
Author Information
1. Department of Pathology, College of Medicine, Chosun University, Gwangju 61501, Korea.
- Publication Type:Original Article
- Keywords:
Apoptosis;
CHOP;
DR5;
Gastric cancer;
MDL-12330A;
TRAIL
- MeSH:
Adenylyl Cyclases;
Apoptosis*;
Cell Death;
Cell Line;
Cell Survival;
Humans;
Immunoblotting;
Stomach Neoplasms*;
Tumor Necrosis Factor-alpha;
Up-Regulation*
- From:The Korean Journal of Physiology and Pharmacology
2017;21(4):397-405
- CountryRepublic of Korea
- Language:English
-
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 (~20 µM), MDL-12330A mainly induced apoptotic death whereas at concentrations greater than 20 µM, 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.
