Comparison of 2-methoxyestradiol and methotrexate effects on non-Hodgkin's B-cell lymphoma.

Abstract:

PURPOSE:Methotrexate (MTX) is the most commonly used chemotherapeutic agent to treat primary central nervous system lymphoma (PCNSL) and intraocular lymphoma (IOL). 2-methoxyestradiol (2ME2) is a potent antitumor and anti-angiogenesis agent which, unlike other cytotoxic drugs, has minimal toxicity. In this study, anti-proliferative, apoptotic, and cell-cycle effects of 2ME2 and MTX were compared to evaluate 2ME2 efficacy in human lymphoma cells, models for non-Hodgkin B cell lymphomas. METHODS:The cells were cultured and incubated with varying concentrations of 2ME2 or MTX. A tetrazolium-based colorimetric assay was used to quantify the anti-proliferative effects of 2ME2 and MTX using a microplate reader. To detect apoptotic and cell cycle distribution changes induced by 2ME2 and MTX, the cells were stained with Annexin V-FITC and/or propidium iodide (PI) and analyzed by flow cytometry. RESULTS:Lymphoma cell proliferation was inhibited by 50% at concentrations ranging from 0.4 to 1 microM for 2ME2 and 0.06 to 0.2 microM for MTX. Induction of apoptosis by 2ME2 and MTX was observed in the tested cells. 2ME2 was a G2/M-phase specific blocker whereas MTX was an S-phase specific blocker in cell cycle analyses. At 1 microM concentration, 2ME2 and MTX showed similar anti-proliferative effect on the lymphoma cell lines. In previously reported studies, for normal endothelial cells, 1 microM 2ME2 showed no appreciable toxicity, while MTX at this same concentration exhibited significant cytotoxicity. 2ME2 at a therapeutic target concentration of 1 mu M may be an effective and relatively non-toxic drug for the treatment of PCNSL with IOL. CONCLUSIONS:Our study of the effect of 2ME2 and MTX on anti-proliferation, apoptosis, and cell cycling suggests that 2ME2 is a potential agent for treating PCNSL and IOL.

journal_name

Curr Eye Res

journal_title

Current eye research

authors

Park J,Franco RS,Augsburger JJ,Banerjee RK

doi

10.1080/02713680701473244

subject

Has Abstract

pub_date

2007-07-01 00:00:00

pages

659-67

issue

7-8

eissn

0271-3683

issn

1460-2202

pii

781950572

journal_volume

32

pub_type

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