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Induction of apoptosis or necrosis in human endometrial cancer cells by 2-Methoxyestradiol
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Genetics and Pathology.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Genetics and Pathology.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.
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2004 (English)In: Anticancer Research, ISSN 0250-7005, E-ISSN 1791-7530, Vol. 24, no 6, 3983-3990 p.Article in journal (Refereed) Published
Abstract [en]

BACKGROUND:

We investigated the effects of 2methoxyestradiol (2-ME), an endogenous estrogenic metabolite, on human endometrial cancer HEC-1-A and RL-95-2 cell lines.

MATERIALS AND METHODS:

After exposure of HEC-1-A and RL-95-2 cells to 2-ME, the morphological changes were evaluated by acridine orange staining and transmission electron microscopy. Cell cycle progress, apoptosis and necrosis were assessed by flow cytometry, DNA fragmentation and Western blot.

RESULTS:

2-ME inhibited cell growth by blocking the S- and G2/M-phase in both cell lines, by inducing apoptosis in HEC-1-A cells and by causing necrosis in RL-95-2 cells. Apoptosis, on HEC-1-A cells, was accompanied by an increased expression of iNOS and STAT1. This apoptotic effect was prevented by the iNOS inhibitor 1400W and eliminated by the caspase inhibitor Z-VAD-FMK. Necrosis, on RL-95-2 cells, was due to a severe disruption of the mitochondrial membrane potential. 2-ME had no significant effect on normal human endometrial cells.

CONCLUSION:

The data suggest that 2-ME has an antitumor effect on human endometrial carcinoma cells (HEC-1-A and RL-95-2) and may contribute as a new therapeutic agent for endometrial cancer patients.

Place, publisher, year, edition, pages
2004. Vol. 24, no 6, 3983-3990 p.
National Category
Medical and Health Sciences
Identifiers
URN: urn:nbn:se:uu:diva-92134PubMedID: 15736443OAI: oai:DiVA.org:uu-92134DiVA: diva2:165104
Available from: 2004-10-22 Created: 2004-10-22 Last updated: 2017-12-14Bibliographically approved
In thesis
1. Antitumor Activities of 2-Methoxyestradiol on Cervical and Endometrial Cancers In Vitro and In Vivo
Open this publication in new window or tab >>Antitumor Activities of 2-Methoxyestradiol on Cervical and Endometrial Cancers In Vitro and In Vivo
2004 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

2-Methoxyestradiol (2-ME), a metabolite of 17β-estradiol, is a potent antitumor and antiangiogenesis agent in vitro and in vivo. This study aimed to investigate the effects of 2-ME on human cervical and endometrial cancers in vitro and in vivo. Human cervical cancer HeLaS3 cells, endometrial cancer HEC-1-A and RL-95-2 cells, and severe combined immune deficient (SCID) mice were used. On cervical cancer HeLaS3 cells, 2-ME inhibited the cell growth which is accompanied by apoptosis via iNOS pathway and by G2/M cell cycle arrest. 2-ME had slight effects on normal cervical epithelial cells. In vivo on SCID mice, 2-ME (75 mg/kg p.o.) inhibited the growth of human cervical carcinoma by 34% (p < 0.05) and showed slight side effects to liver and spleen. On human endometrial cancer cells (HEC-1-A and RL-95-2 cells), 2-ME inhibited the growth by blocking cell cycle progress in S- and G2/M-phase in both cell types, and by inducing apoptosis in HEC-1-A cells and by causing necrosis in RL-95-2 cells. 2-ME had no effects on normal endometrial cells. The apoptotic effect, in HEC-1-A cells, was prevented by iNOS-inhibitor 1400W and eliminated by Caspase-inhibitor Z-VAD-FMK. The necrosis, on RL-95-2 cells, was due to a severe disruption of the mitochondrial membrane potential. Unfortunately, 2-ME had no significant effects on endometrial cancer xenografts. It showed slight toxicity to liver, spleen and proliferative effect on uterus. In conclusion, 2-ME inhibits the growth of human cervical and endometrial cancer cells in vitro. However, a weaker anti-tumor effect was observed in our animal model and 2-ME was slightly toxic to liver and spleen. Considering the proliferative effect on uterus, 2-ME might not be a suitable therapeutic agent in gynecological tumors.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2004. 62 p.
Series
Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 0282-7476 ; 1374
Keyword
Obstetrics and gynaecology, 2-Methoxyestradiol, HeLaS3 cells, HEC-1-A cells, RL-95-2 cells, cervical cancer, endometrial cancer, Obstetrik och kvinnosjukdomar
National Category
Obstetrics, Gynecology and Reproductive Medicine
Identifiers
urn:nbn:se:uu:diva-4554 (URN)91-554-6039-9 (ISBN)
Public defence
2004-11-12, Rosénsalen, Ing 96, Kvinnokliniken, Akademiska sjukhuset, 751 85 Uppsala, 09:15
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Available from: 2004-10-22 Created: 2004-10-22 Last updated: 2011-02-09Bibliographically approved

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