OBJECTIVE: The estrogen metabolite 2-methoxyestradiol has shown antitumorigenic action in some epithelial tumors. In the present work we investigate its effects in ovarian cancer used alone or in combination with other apoptotic-inducing reagents such as tumor necrosis factor-related apoptosis-inducing ligand. METHODS: To assess the effect of 2-methoxyestradiol, dose response and time courses in ovarian cancer and normal cells were conducted. Apoptosis was confirmed through DNA laddering, by flow cytometry, and Western blotting of proteins involved in the apoptotic cascade. RESULTS: 2-Methoxyestradiol induced apoptosis in ovarian cancer cells but not in normal counterparts. 2-Methoxyestradiol activates both the intrinsic and extrinsic apoptotic pathways. 2-Methoxyestradiol-mediated apoptosis involves reactive oxygen species generation and caspase-dependent and caspase-independent mechanisms. We also demonstrate that 2-methoxyestradiol selectively induces an additive/synergistic apoptotic response in ovarian cancer cells when used in combination with tumor necrosis factor-related apoptosis-inducing ligand. CONCLUSIONS: 2-Methoxyestradiol, alone or in combination with tumor necrosis factor-related apoptosis-inducing ligand, should be considered as a potential treatment for ovarian cancer.
OBJECTIVE: The estrogen metabolite 2-methoxyestradiol has shown antitumorigenic action in some epithelial tumors. In the present work we investigate its effects in ovarian cancer used alone or in combination with other apoptotic-inducing reagents such as tumor necrosis factor-related apoptosis-inducing ligand. METHODS: To assess the effect of 2-methoxyestradiol, dose response and time courses in ovarian cancer and normal cells were conducted. Apoptosis was confirmed through DNA laddering, by flow cytometry, and Western blotting of proteins involved in the apoptotic cascade. RESULTS: 2-Methoxyestradiol induced apoptosis in ovarian cancer cells but not in normal counterparts. 2-Methoxyestradiol activates both the intrinsic and extrinsic apoptotic pathways. 2-Methoxyestradiol-mediated apoptosis involves reactive oxygen species generation and caspase-dependent and caspase-independent mechanisms. We also demonstrate that 2-methoxyestradiol selectively induces an additive/synergistic apoptotic response in ovarian cancer cells when used in combination with tumor necrosis factor-related apoptosis-inducing ligand. CONCLUSIONS: 2-Methoxyestradiol, alone or in combination with tumor necrosis factor-related apoptosis-inducing ligand, should be considered as a potential treatment for ovarian cancer.
Authors: M Cuello; S A Ettenberg; A S Clark; M M Keane; R H Posner; M M Nau; P A Dennis; S Lipkowitz Journal: Cancer Res Date: 2001-06-15 Impact factor: 12.701
Authors: Juan Shi; Dexian Zheng; Yanxin Liu; Mai Har Sham; Paul Tam; Farzin Farzaneh; Ruian Xu Journal: Cancer Res Date: 2005-03-01 Impact factor: 12.701
Authors: M Cuello; A O Coats; I Darko; S A Ettenberg; G J Gardner; M M Nau; J R Liu; M J Birrer; S Lipkowitz Journal: Cell Death Differ Date: 2004-05 Impact factor: 15.828
Authors: Giovanni D Aletti; Mary M Gallenberg; William A Cliby; Aminah Jatoi; Lynn C Hartmann Journal: Mayo Clin Proc Date: 2007-06 Impact factor: 7.616
Authors: Igor Hrgovic; Johannes Kleemann; Monika Doll; Carmen Loquai; Florian Weid; Frank Louwen; Nadja Zoeller; Stefan Kippenberger; Roland Kaufmann; Markus Meissner Journal: Mol Clin Oncol Date: 2021-05-23
Authors: Scott D Hargrave; Anna M Joubert; Barry V L Potter; Wolfgang Dohle; Sumari Marais; Anne E Mercier Journal: Molecules Date: 2022-06-14 Impact factor: 4.927