Vitamin D Analog EB1089 Induces Apoptosis in a Subpopulation of SGC-7901 Gastric Cancer Cells Through a Mitochondrial-Dependent Apoptotic Pathway

Abstract

Gastric cancer is the second leading cause of cancer death worldwide. Cancer stem-like side population (SP) cells may be important factors that hinder efficacy of chemopreventative and chemotherapeutic approaches in gastric cancer. EB1089 is an antitumor agent that has been used in many cancers; however, no reports to date have determined the effects of EB1089 in gastric cancer. In our study, SP and main population (MP) cells were isolated from 4 gastric cancer cell lines in different stages of differentiation by flow cytometry (FCM) and confirmed by reverse transcription polymerase chain reaction (RT-PCR) and Western blot. EB1089 decreased the proliferation, increased apoptosis, and induced mitochondrial damage in the SP cells isolated from 1 cell type (SGC-7901), but not MP cells, through increased Bax and decreased Bcl-2 and Bcl-xL protein expression. This protein expression pattern induced the activation of caspase-3 and caspase-9. The effects of EB1089 on SGC-7901 SP cells were blocked by treating cells with vitamin D receceptor (VDR) siRNA or butin (an inhibitor of the mitochondrial apoptosis pathway). Our results suggest that EB1089 targets SGC-7901 SP cells through a mitochondrial apoptosis pathway. However, further studies are needed to elucidate the signal transduction between VDR and the mitochondrial apoptosis pathway.