Newly synthesized (E)-4-(2-chloro-1-(2-chloro-benzyl)-1H-indol-3-yl)but-3-en-2-one (SBA) induces apoptotic cell death through Fas-FasL and mitochondria-mediated pathways in human oral carcinoma SCC-4 cells

SBA, (E)-4-(2-chloro-1-(2-chloro-benzyl)-1H-indol-3-yl)but-3-en-2-one, is a derivative of natural product, named 4,4'-dimethoxychalcone. In this study, the impact of newly synthesized SBA on cell apoptosis was investigated in human oral cancer SCC-4 cells in vitro. The results showed that SBA decreased cell viability, induced S and G2/M phase arrest, and induced apoptosis in SCC-4 cells. SBA also increased ROS production, reduced mitochondrial membrane potential, and activated caspase-9 and caspase-3 in a dose-dependent manner. SBA induced the upregulation of Chk1 and Chk2 expressions, while it resulted in a reduction of cdc2 and Cyclin B1 levels. SBA also increased the levels of Fas, FasL, FADD, caspase-8, and BID. Moreover, it increased the expression of Bad, Bax, cytochrome c, AIF, EndoG, caspase-9, and caspase-3, while reducing the expression of Bcl-2, Bcl-xL, and XIAP in SCC-4 cells. Taken together, these findings suggest that SBA induces cytotoxicity in SCC-4 cells via Fas-FasL- and mitochondria-mediated pathways.