Induction of apoptosis and G2/M arrest by 2-methoxyestradiol in human cervical cancer HeLaS3 cells.
2004 (English)In: Anticancer Res, ISSN 0250-7005, Vol. 24, no 2B, 873-80 p.Article in journal (Refereed) Published
BACKGROUND: It has been demonstrated that 2-Methoxyestradiol (2-ME), one of the estrogen metabolites, induces apoptosis in many different tumor cell lines. In the present study, the effects of 2-ME on human cervical cancer HeLaS3 cells and on normal cervical epithelial cells were evaluated. MATERIALS AND METHODS: Acridine orange staining, DNA fragmentation arrays and flow cytometry were used to measure the apoptosis and cell cycle progression. In addition, the effect of 2-ME on expression of iNOS was measured by Western blot. RESULTS: 2-ME inhibited the growth of HeLaS3 cells. This growth inhibition was accompanied by apoptosis and G2/M cell cycle arrest. 2-ME increased the expression of iNOS in parallel with apoptosis. Moreover, apoptosis was prevented by the iNOS inhibitor 1400W. 2-ME treatment resulted in a slight increase of the G2/M population, but no apoptosis, in normal cervical epithelial cells. There was no synergetic effect between E2 and 2-ME. CONCLUSION: 2-ME induced apoptosis via the iNOS pathway and caused G2/M cell cycle arrest in human cervical cancer HeLaS3 cells, but showed only slight effects on normal cervical epithelial cells. These data suggest that 2-ME might be an adjuvant agent in the treatment of cervical cancer.
Place, publisher, year, edition, pages
2004. Vol. 24, no 2B, 873-80 p.
Adenocarcinoma/*drug therapy/pathology, Apoptosis/*drug effects, Cell Cycle/*drug effects, Cell Division/drug effects, Cervix Neoplasms/*drug therapy/pathology, Cervix Uteri/cytology/drug effects, Epithelial Cells/cytology/drug effects, Estradiol/*analogs & derivatives/*pharmacology, Female, G2 Phase/drug effects, Hela Cells, Humans, Mitosis/drug effects, Research Support; Non-U.S. Gov't
IdentifiersURN: urn:nbn:se:uu:diva-73059PubMedID: 15161040OAI: oai:DiVA.org:uu-73059DiVA: diva2:100970