2-Methoxyestradiol blocks cell-cycle progression at the G2/M phase and induces apoptosis in human acute T lymphoblastic leukemia CEM cells  

作　　者：Xueya Zhang Haobo Huang Zhenshu Xu Rong Zhan 

机构地区：[1]Department of Hematology, Fujian Medical University Union Hospital, Fuzhou 350001, China [2]Department of Transfusion, Fujian Medical University Union Hospital, Fuzhou 350001, China [3]Department of Hematology, Fujian Medical University Second Hospital, Quanzhou 362000, China

出　　处：《Acta Biochimica et Biophysica Sinica》2010年第9期615-622,共8页生物化学与生物物理学报（英文版）

摘　　要：2-Methoxyestradiol （2-ME2） is an endogenous metabolite of 17β-estradioi （E2） with estrogen receptor-independent anti-cancer activity. The current study sought to determine the mechanism of anti-cancer activity of 2-ME2 in human acute T lymphoblastic leukemia CEM cells. Results showed that 2-ME2 markedly suppressed proliferation of CEM cells in a time- and dose-dependent manner. 2-ME2-treated CEM cells underwent typical apoptotic changes. Exposure to 2-ME2 led to G2/M phase cell-cycle arrest, which preceded apoptosis characterized by the appearance of a sub-G1 cell population. In addition, cytosolic cytochrome c release, increased procaspase-9 and -3 expressions, poly（ADP-ribose） polymerase （PARP） cleavage, and induced expression of caspase-8 were detected, suggesting that both the intrinsic apoptotic pathway and extrinsic apoptotic pathway were involved in 2-ME2-induced apoptosis. Moreover, the expression level of p21 protein was upregulated, whereas Bcl-2 and dysfunctional p53 protein were downregulated, which also contributed to 2-ME2-induced apoptosis. Our findings revealed that 2-ME2 might be a potent natural candidate for chemotherapeutic treatment of human acute T lymphoblastic leukemia when the precise effects of 2-ME2 were investigated further in other T leukemia cell lines and in primary T-cell leukemias.2-Methoxyestradiol （2-ME2） is an endogenous metabolite of 17β-estradioi （E2） with estrogen receptor-independent anti-cancer activity. The current study sought to determine the mechanism of anti-cancer activity of 2-ME2 in human acute T lymphoblastic leukemia CEM cells. Results showed that 2-ME2 markedly suppressed proliferation of CEM cells in a time- and dose-dependent manner. 2-ME2-treated CEM cells underwent typical apoptotic changes. Exposure to 2-ME2 led to G2/M phase cell-cycle arrest, which preceded apoptosis characterized by the appearance of a sub-G1 cell population. In addition, cytosolic cytochrome c release, increased procaspase-9 and -3 expressions, poly（ADP-ribose） polymerase （PARP） cleavage, and induced expression of caspase-8 were detected, suggesting that both the intrinsic apoptotic pathway and extrinsic apoptotic pathway were involved in 2-ME2-induced apoptosis. Moreover, the expression level of p21 protein was upregulated, whereas Bcl-2 and dysfunctional p53 protein were downregulated, which also contributed to 2-ME2-induced apoptosis. Our findings revealed that 2-ME2 might be a potent natural candidate for chemotherapeutic treatment of human acute T lymphoblastic leukemia when the precise effects of 2-ME2 were investigated further in other T leukemia cell lines and in primary T-cell leukemias.

关 键 词：2-METHOXYESTRADIOL human acute T lymphoblastic leukemia cell proliferation cell apoptosis cell cycle 

分 类 号：Q255[生物学—细胞生物学] S858.315.3[农业科学—临床兽医学]