ABSTRACT
2-Methoxyestradiol-bis-sulphamate is a bis-sulphamoylated derivative of the naturally occurring 17-beta-estradiol metabolite namely 2-methoxyestradiol. 2-Methoxyestradiol-bis-sulphamate is regarded as a potential anticancer drug with increased antiproliferative activity when compared to 2-methoxyestradiol. The aim of this pilot in vitro study was to determine the influence of 2-methoxyestradiol-bis-sulphamate on cell growth, morphology and possible induction of certain types of cell death in the SNO esophageal carcinoma cell line. A dose-dependent study (0.2-1.0 microM) was conducted with an exposure time of 24 hours. Data revealed that 2-methoxyestradiol-bis-sulphamate reduced cell numbers statistically significantly to 74% after exposure to 0.4 microM of the drug. Morphological studies including light microscopy demonstrated hallmarks of apoptosis, while fluorescent microscopy revealed both the presence of apoptosis and autophagy as types of cell death being induced in SNO cells after 24 hours of exposure to 0.4 microM 2-methoxyestradiol-bis-sulphamate.
Subject(s)
Humans , Apoptosis , Autophagy , Cell Count , Carcinoma, Squamous Cell/pathology , Cell Cycle , Cell Division , Cell Line, Tumor , Dose-Response Relationship, Drug , Estriol/analogs & derivatives , Estriol/pharmacology , Esophageal Neoplasms/pathologyABSTRACT
Proteins of the B-cell lymphoma 2 family are crucial for the regulation of apoptosis. B-cell lymphoma 2-associated X is a pro-apoptotic protein, while B-cell lymphoma 2 protein opposes apoptosis. The influence of 1 microM 2-methoxyestradiol was investigated on the expression levels of these two proteins in MCF-7 cells. 2-Methoxyestradiol exposure did not influence B-cell lymphoma 2 protein expression levels after 24 h of exposure. In contrast, B-cell lymphoma 2-associated X protein levels were significantly reduced. An improved differential interference contrasting technique revealed compromised cell density and the presence of a mitotic block in exposed cells. The study proposes that the influence of 2-methoxyestradiol on the expression of these proteins may be time- and cell type dependent and thus not evident d uring the mitotic block observed. Investigation of the regulation of the B-cell lymphoma 2 family will allow researchers to consider signaling pathways for diseases where apoptosis can potentially be controlled.