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Effects of 2-methoxyestradiol on endometrial carcinoma xenografts
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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2007 (English)In: Journal of Cancer Research and Clinical Oncology, ISSN 0171-5216, E-ISSN 1432-1335, Vol. 133, no 5, 315-320 p.Article in journal (Refereed) Published
Abstract [en]

Purpose: We have previously demonstrated that 2-methoxyestradiol (2-ME) inhibits the growth of human endometrial cancer HEC-1-A and RL-95-2 cells in vitro. In this study, we examined the effects of 2-ME on human endometrial carcinoma in severe combined immune deficient (SCID) mice. The potential side effects of 2-ME on SCID mice were also investigated. Methods: Severe combined immune deficient mice were injected with HEC-1-A cells (1 × 10 6/mouse) and a 18 day administration of 2-ME was followed after 1 week cell implantation. Tumor volume, weight, body weight and blood chemistry were determined. Tumor tissues were examined with an antibody against the proliferative cell nuclear antigen (PCNA) and Ki-67. Liver, spleen, kidney, heart, lung and uterus were screened by pathological examinations. Results: 2-ME (100 mg/kg p.o.) did not inhibit the growth of human endometrial carcinoma as compared to control. Necrotic areas were similar in both 2-ME-treated and -untreated tumor tissues. The expressions of PCNA and Ki-67 were similar in 2-ME-treated and untreated tumor sections. The wet weight of uterus was increased to more than threefold. The epithelial cells and glands in endometrium were increased. No significant difference was detected in blood AST, ALT and BUN. Conclusions: 2-ME has no antitumor effects on human endometrial carcinoma in our animal model. Its proliferative effects on endometrium and uterus might limit its use in gynecological cancers.

Place, publisher, year, edition, pages
2007. Vol. 133, no 5, 315-320 p.
Keyword [en]
2-Methoxyestradiol, Human endometrial carcinoma, SCID mice
National Category
Medical and Health Sciences
Identifiers
URN: urn:nbn:se:uu:diva-92136DOI: 10.1007/s00432-006-0173-xISI: 000245294700005PubMedID: 17165027OAI: oai:DiVA.org:uu-92136DiVA: diva2:165106
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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