8-chloroadenosine 3 ', 5 '-monophosphate induces apoptosis of multiple myeloma cells catalyzed by arsenic trioxide

Objective To investigate the response of multiple myeloma (MM) cells to 8-chloroadenosine 3',5'-monophosphate (8-Cl-cAMP) and the impact of arsenic trioxide (As2O3) on the above reaction.Methods MM-derived cell lines RPMI8226 and U266 were used as in vitro models.Cell apoptosis was evaluated according to cellular morphology and DNA content measured by flow cytometry.Meanwhile,rhodamine 123 (Rh123) staining and flow cytometry assay were used to detect the changes of mitochondrial transmembrane potentials (△ψm) in MM cells before and after the treatment.The synergic effects of 8-Cl-cAMP and As2O3 were evaluated by King' s formula.Results The 8-Cl-cAMP could induce growth inhibition of RPMI8226 and U266 cells in dose and time-related manners.The 8-Cl-cAMP could trigger apoptosis and △ψm collapse in MM cells through cellular morphology and flow cytometry analysis.As2O3 accelerated 8-Cl-cAMP-mediated apoptosis of RPMI8226 cells,but there were few synergic effects observed.Conclusion 8-Cl-cAMP could induce cell proliferation inhibition and apoptosis in MM cells.Mitochondria may be one of targets in 8-Cl-cAMP-mediated apoptosis.Furthermore,As2O3 catalyzes 8-Cl-cAMP-induced apoptosis. Key words: Multiple myeloma;  Apoptosis;  Membrane potential, mitochondrial;  Arsenic trioxide; 8-chloroadenosine 3', 5'-monophosphate