Inhibition of normal and experimental angiotumor endothelial cell proliferation and cell cycle progression by 2-methoxyestradiol

F. Reiser, D. Way, Michael J Bernas, Marlys H Witte, C. Witte

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Abstract

With rapid growth and metabolism, aggressive cancers require an extensive vascular network, termed tumor angiogenesis. The body produces a variety of natural angiogenic inhibitors, among which is the mammalian estrogen metabolite, 2-methoxyestradiol (2-MeOE2). In this study, we compared the effects of 2-MeOE2 on a human umbilical vein cell line (HUVEC- C) and on an immortal, angiotumor-producing rat sinusoidal endothelial cell line (RSE-1). In vitro, the effects of varying concentrations of 2-MeOE2 from 0.01-100.0 μM were measured with cell counts and compared to control cells. HUVEC-C had an ED50 -3.5 μM with ~27% inhibition of cell growth whereas RSE-1 had an ED50 ~2.2 μM with ~50% inhibition of cell growth compared with controls. The lowest concentration with maximal effect was 10.0 μM 2-MeOE2 for both cell lines. Using this concentration, flow cytometric analysis of cell cycles was performed with propidium iodide stained DNA of HUVEC-C and RSE-1 at 24 and 48 hr. Both demonstrated a significant (P < 0.0001) block at G2M of the cell cycle. At 48 hr, HUVEC-C had 32% of cells in G2M (control = 9% G2M), and RSE-1 had 36% of cells in G2M (control = 18% G2M). These findings demonstrate a strong in vitro antiproliferative effect of 2-MeOE2 on normal dividing endothelial as well as angiotumor cells mediated through a cell cycle-specific block at G2M. The antiendothelial, antianglotumor effect of 2-MeOE2 supports its potential as a therapeutic agent against solid organ cancers, benign or malignant vascular growths, and other pathologic states dependent on angiogenesis.

Original languageEnglish (US)
Pages (from-to)211-216
Number of pages6
JournalProceedings of the Society for Experimental Biology and Medicine
Volume219
Issue number3
StatePublished - Dec 1998

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Endothelial cells
Cell proliferation
Cell Cycle
Endothelial Cells
Cells
Cell Proliferation
Cell growth
Growth
Cell Line
Blood Vessels
Angiogenesis Inhibitors
Propidium
Neoplasms
Metabolites
Umbilical Veins
Metabolism
Rats
Tumors
Estrogens
2-methoxyestradiol

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

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title = "Inhibition of normal and experimental angiotumor endothelial cell proliferation and cell cycle progression by 2-methoxyestradiol",
abstract = "With rapid growth and metabolism, aggressive cancers require an extensive vascular network, termed tumor angiogenesis. The body produces a variety of natural angiogenic inhibitors, among which is the mammalian estrogen metabolite, 2-methoxyestradiol (2-MeOE2). In this study, we compared the effects of 2-MeOE2 on a human umbilical vein cell line (HUVEC- C) and on an immortal, angiotumor-producing rat sinusoidal endothelial cell line (RSE-1). In vitro, the effects of varying concentrations of 2-MeOE2 from 0.01-100.0 μM were measured with cell counts and compared to control cells. HUVEC-C had an ED50 -3.5 μM with ~27{\%} inhibition of cell growth whereas RSE-1 had an ED50 ~2.2 μM with ~50{\%} inhibition of cell growth compared with controls. The lowest concentration with maximal effect was 10.0 μM 2-MeOE2 for both cell lines. Using this concentration, flow cytometric analysis of cell cycles was performed with propidium iodide stained DNA of HUVEC-C and RSE-1 at 24 and 48 hr. Both demonstrated a significant (P < 0.0001) block at G2M of the cell cycle. At 48 hr, HUVEC-C had 32{\%} of cells in G2M (control = 9{\%} G2M), and RSE-1 had 36{\%} of cells in G2M (control = 18{\%} G2M). These findings demonstrate a strong in vitro antiproliferative effect of 2-MeOE2 on normal dividing endothelial as well as angiotumor cells mediated through a cell cycle-specific block at G2M. The antiendothelial, antianglotumor effect of 2-MeOE2 supports its potential as a therapeutic agent against solid organ cancers, benign or malignant vascular growths, and other pathologic states dependent on angiogenesis.",
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AU - Witte, C.

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