학술논문
MDL-12330A potentiates TRAIL-induced apoptosis in gastric cancer cells through CHOP-mediated DR5 upregulation
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- 영문명
- MDL-12330A potentiates TRAIL-induced apoptosis in gastric cancer cells through CHOP-mediated DR5 upregulation
- 발행기관
- 대한생리학회-대한약리학회
- 저자명
- Sung-Chul Lim Song Iy Han
- 간행물 정보
- 『The Korean Journal of Physiology & Pharmacology』제21권 제4호, 397~405쪽, 전체 9쪽
- 주제분류
- 의약학 > 의학일반
- 파일형태
- 발행일자
- 2017.01.01
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국문 초록
영문 초록
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.
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