Effect of apogossypolone on induction apoptosis in multiple myeloma cells and its mechanisms.
- Author:
Jie LIN
1
;
Yong-Ji WU
;
Da-Jun YANG
;
Yong-Qiang ZHAO
Author Information
1. Department of Geriatric Hematology, PLA General Hospital, Beijing 100853, China.
- Publication Type:Journal Article
- MeSH:
Apoptosis;
drug effects;
Caspase 3;
metabolism;
Caspase 9;
metabolism;
Cell Line, Tumor;
Cell Proliferation;
drug effects;
Gossypol;
analogs & derivatives;
pharmacology;
Humans;
Proto-Oncogene Proteins c-bcl-2;
metabolism;
bcl-X Protein;
metabolism
- From:
Journal of Experimental Hematology
2009;17(1):92-98
- CountryChina
- Language:Chinese
-
Abstract:
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.
