Induction of apoptosis or necrosis in human endometrial cancer cells by 2-Methoxyestradiol
2004 (English)In: Anticancer Research, ISSN 0250-7005, Vol. 24, no 6, 3983-3990 p.Article in journal (Refereed) Published
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.
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.
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.
Medical and Health Sciences
IdentifiersURN: urn:nbn:se:uu:diva-92134PubMedID: 15736443OAI: oai:DiVA.org:uu-92134DiVA: diva2:165104