2,3 ', 4,4' - Tetramethoxy Biphenyl In Vitro Induced Apoptosis Of Mgc-803 Mechanism Of Preliminary Research

This study was designed to investigate the effect of 2,4,3',4'-tetramethoxy-biphenyl (TMBP) on human gastric cancer MGC-803 cells. Twelve intermediates of biphenyl compounds were synthesized when protosappanin A were prepared. The cytotoxic activity of these compounds on MGC-803 cells was tested by MTT assay. We found that the IC50 value of TMBP is the lowest among these compounds. Therefore, we attempted to detect the molecular mechanisms of TMBP-mediated tumor cell death through clonogenic assay, staining with Hoechst 33258, DNA fragmentation assay, Western blot analysis and flow cytometry assay. Studies on MGC-803 cells treated with TMBP showed that TMBP inhibited the proliferation of MGC-803 cells in a time- and dose-dependent manner. The induction of apoptosis by TMBP was accompanied by the loss of mitochondrial membrane potential (ΔΨm), cytochrome c release and activation of caspase cascade, resulting in the cleavage of some specific substrates for caspase-3 such as poly (ADP-ribose) polymerase (PARP). Taken together, N-acetylcysteine attenuated MGC-803 cell death induced by TMBP (p<0.05). The finding indicated that TMBP-mediated oxidative injury may act as upstream change, trigger ROS release. In conclusion, these findings showed that TMBP may induce the apoptosis of MGC-803 through a mitochondrial/caspase pathway, suggesting its possible use for treating human cancers.