Induction of apoptosis and G2/M arrest by 2-methoxyestradiol in human cervical cancer HeLaS3 cells.
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.


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.


CONCLUSIONS
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.
Li
Li
L
Department of Women's and Children's Health, Section for Obstetrics and Gynecology, Uppsala University, 751 85 Uppsala, Sweden.
Bu
Shizhong
S
Bäckström
Torbjörn
T
Landström
Maréne
M
Ulmsten
Ulf
U
Fu
Xin
X
D000077584:2-Methoxyestradiol; D000230:Adenocarcinoma / Q000188:drug therapy* / Q000473:pathology; D017209:Apoptosis / Q000187:drug effects*; D002453:Cell Cycle / Q000187:drug effects*; D002455:Cell Division / Q000187:drug effects; D002584:Cervix Uteri / Q000166:cytology / Q000187:drug effects; D004847:Epithelial Cells / Q000166:cytology / Q000187:drug effects; D004958:Estradiol / Q000031:analogs & derivatives* / Q000494:pharmacology*; D005260:Female; D016195:G2 Phase / Q000187:drug effects; D006367:HeLa Cells; D006801:Humans; D008938:Mitosis / Q000187:drug effects; D002583:Uterine Cervical Neoplasms / Q000188:drug therapy* / Q000473:pathology
D004958:Estradiol; D000077584:2-Methoxyestradiol