A Synthetic Chenodeoxycholic Acid Derivative, HS-1200-induced Apoptosis of RBL-2H3 Cells / 대한해부학회지

ABSTRACT

Bile acids and synthetic bile acid derivatives induced apoptosis in various kinds of cancer cells and anticancer effects. Although synthetic chenodeoxycholic acid (CDCA) derivatives have been demonstrated to induce apoptosis of various cancer cells, there is no report on their effect on RBL-2H3 basophilic leukemia cell line to date. Therefore, this study was undertaken to examine in vitro effects of cytotoxicity and growth inhibition, and the molecular mechanism underlying induction of apoptosis in RBL-2H3 cells treated with a synthetic CDCA derivative, HS-1200. The viability and the growth inhibition of RBL-2H3 cells were assessed by MTT assay and clonogenic assay respectively. The Hoechst staining and DNA electrophoresis were conducted to observe RBL-2H3 cells undergoing apoptosis. RBL-2H3 cells were treated with HS-1200, and Western blotting, immunocytochemistry, confocal microscopy, DNA hypoploidy assay, MMP activity and proteasome activity were performed. HS-1200 treatment of RBL-2H3 cells resulted in a time- and does-dependent decrease of cell viability and a does-dependent inhibition of cell growth, and induced apoptotic cell death. Furthermore, HS-1200 treatment result in the alteration of G1 cell cycle-related proteins. And tested RBL-2H3 cells showed several lines of apoptotic manifestation.We presented data indicating that HS-1200 induces apoptois via the proteasome, mitochondria and caspase pathway, and induces the alteration of the G1 cell cycle-related proteins in RBL-2H3 cells. Therefore our data provide the possibility that HS-1200 could be as a novel therapeutic strategy in the allergy treatment.