Dual effect of 2-methoxyestradiol on cell cycle events in human osteosarcoma 143B cells.
We have demonstrated for the first time that the steroid metabolite, 2-methoxyestradiol (2-ME) is a powerful growth inhibitor of human osteosarcoma 143 B cell line by pleiotropic mechanisms involving cell cycle arrest at two different points and apoptosis. The ability of 2-ME to inhibit cell cycle at the respective points has been found concentration dependent. 1 microM 2-ME inhibited cell cycle at G1 phase while 10 microM 2-ME caused G2/M cell cycle arrest. As a natural estrogen metabolite 2-ME is expected to perturb the stability of microtubules (MT) in vivo analogously to Taxol--the MT binding anticancer agent. Contrary to 2-ME, Taxol induced accumulation of osteosarcoma cells in G2/M phase of cell cycle only. The presented data strongly suggest two different mechanisms of cytotoxic action of 2-ME at the level of a single cell.
Department of Medical Chemistry, Medical University of Gdańsk, Poland.
Justyna
J
Gołebiewska
Piotr
P
Rozwadowski
Jan Henryk
JH
Spodnik
Narcyz
N
Knap
Takashi
T
Wakabayashi
Michał
M
Woźniak
D000077584:2-Methoxyestradiol; D002453:Cell Cycle / Q000502:physiology*; D004958:Estradiol / Q000031:analogs & derivatives* / Q000494:pharmacology*; D006801:Humans; D018613:Microscopy, Confocal; D008870:Microtubules / Q000378:metabolism; D012516:Osteosarcoma / Q000188:drug therapy*; D014404:Tubulin / Q000378:metabolism; D014407:Tumor Cells, Cultured
D014404:Tubulin; D004958:Estradiol; D000077584:2-Methoxyestradiol