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Induction of apoptosis and G2/M arrest by 2-Methoxyestradiol in human cervical cancer HeLaS3 cells
Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Women's and Children's Health.
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2004 In: Anticancer Research, Vol. 24, no 2, 873-880 p.Article in journal (Refereed) Published
Place, publisher, year, edition, pages
2004. Vol. 24, no 2, 873-880 p.
Identifiers
URN: urn:nbn:se:uu:diva-92132OAI: oai:DiVA.org:uu-92132DiVA: diva2:165102
Available from: 2004-10-22 Created: 2004-10-22Bibliographically 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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