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


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

X Zhang, H Huang, Z Xu and R. Zhan

Acta Biochimica et Biophysica Sinica, 2010, 42(9), 615-622. DOI: 10.1093/abbs/gmq065

Abstract

2-Methoxyestradiol (2-ME2) is an endogenous metabolite of 17β-estradiol (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.

ASCI-ID: 1071-157