This study was aimed to investigate the effects of
apogossypolone (ApoG2) on proliferative inhibition and apoptotic induction of
multiple myeloma cells and its mechanism. The effects of ApopG2 on cell growth, cell viability, cell cycle and cell apoptosis were determined by
Hoechst 33258 staining,
DNA ladder formation and subdiploid peak analysis respectively. Cleavage of
caspase-3 and
caspase-9 was analyzed by colorimetric assay. Expression of BCL-2 and BCL-XL was detected by flow cytometry. The results indicated that the ApoG2 inhibited
multiple myeloma cell proliferation in dose-and time-dependent manners, with IC(50) value to both U266 and Wusl cells at 0.1 and 0.2 micromol/L at 48 hours
after treatment. ApoG2 effectively inhibited the proliferation of
multiple myeloma cells, the IC(50) value in U266 cells and Wusl cells (at 48 hours) were 0.1 micromol/L and 0.2 micromol/L respectively. ApoG2 could induce the apoptosis of cells of myeloma in a time-dependent manner.The typical apoptotic morphological changes were observed under transmission electron microscope, while
DNA ladder formation and remarkable peak of subdiploid cells appeared. ApoG2 could arrest the myeloma cells in G(2) phase, increasing from 9.7%(0 micromol/L) to 19.6% (10 micromol/L) in U266 cells and 9.8%(0 micromol/L) to 31.7% (10 micromol/L) in Wusl cells. ApoG2 could induce increase of
caspase 9 and
caspase 3 activity and down-regulate the expression of BCL-XL in U266 and Wusl cells, as well as the expression of BCL-2 in Wusl cells. It is concluded that ApoG2 has significant effect of antiproliferation and induction of apoptosis on
multiple myeloma cells in vitro, ant its mechanisms may involve in down-regulation of BCL-2/BCL-XL and in change of cell cycle.