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Updated: Jun 9, 2026
Preparation of Primary Acute Lymphoblastic Leukemia Cells in Different Cell Cycle Phases by Centrifugal Elutriation
Published on: November 10, 2017
2-Methoxyestradiol blocks cell-cycle progression at the G2/M phase and induces apoptosis in human acute T
Xueya Zhang1, Haobo Huang, Zhenshu Xu
1Department of Hematology, Fujian Medical University Union Hospital, Fuzhou, China.
Abstract:
2-Methoxyestradiol (2-ME2) is an endogenous metabolite of 17beta-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 G(2)/M phase cell-cycle arrest, which preceded apoptosis characterized by the appearance of a sub-G(1) 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.
Insights
2-Methoxyestradiol (2-ME2), an estrogen metabolite, effectively inhibits leukemia cell growth and induces apoptosis. It triggers cell-cycle arrest and activates both intrinsic and extrinsic apoptotic pathways, showing potential as a leukemia therapeutic.
Area of Science:
- Oncology
- Molecular Biology
- Biochemistry
Background:
- 2-Methoxyestradiol (2-ME2) is an endogenous metabolite of 17beta-estradiol (E2).
- 2-ME2 exhibits anti-cancer activity independent of estrogen receptors.
- Its mechanism in acute T lymphoblastic leukemia (T-ALL) requires elucidation.
Purpose of the Study:
- To investigate the anti-cancer mechanism of 2-ME2 in human T-ALL CEM cells.
- To determine the effects of 2-ME2 on cell proliferation, cell cycle, and apoptosis.
Main Methods:
- Human T-ALL CEM cells were treated with varying concentrations of 2-ME2.
- Cell proliferation was assessed using proliferation assays.
- Cell cycle distribution and apoptosis were analyzed by flow cytometry.
- Apoptotic pathway markers (cytochrome c, caspases, PARP) and protein expression (p21, Bcl-2, p53) were evaluated.
Main Results:
- 2-ME2 significantly suppressed CEM cell proliferation in a time- and dose-dependent manner.
- 2-ME2 induced G(2)/M cell-cycle arrest and apoptosis, evidenced by sub-G(1) population.
- Activation of both intrinsic (cytochrome c release, caspase-9/-3 activation) and extrinsic (caspase-8 activation) apoptotic pathways was observed.
- Upregulation of p21 and downregulation of Bcl-2 and p53 contributed to apoptosis.
Conclusions:
- 2-ME2 induces apoptosis in human T-ALL CEM cells via both intrinsic and extrinsic pathways.
- Cell-cycle arrest and modulation of key proteins (p21, Bcl-2, p53) are crucial to its mechanism.
- 2-ME2 presents a potential natural therapeutic candidate for T-ALL, warranting further investigation.
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