In vitro effects of 2-methoxyestradiol-bis-sulphamate on the non-tumorigenic MCF-12A cell line

• Published in: Cell biochemistry and function Vol. 28; no. 5; pp. 412 - 419
• Main Authors: Vorster, Christiaan Jacob Johan, Joubert, Anna Margaretha
• Format: Journal Article
• Language: English
• Published: Chichester, UK John Wiley & Sons, Ltd 01.07.2010
• Subjects: 2-methoxyestradiol; 2-methoxyestradiol-bis-sulphamate; Antineoplastic Agents - chemistry; Antineoplastic Agents - therapeutic use; Apoptosis; autophagy; Breast Neoplasms - drug therapy; Breast Neoplasms - ultrastructure; cancer; Cell Division; Cell Line, Tumor; Cyclin B1 - metabolism; Estrenes - chemistry; Estrenes - therapeutic use; Female; Flow Cytometry; G2 Phase; Humans; Time Factors
• ISSN: 0263-6484; 1099-0844
• DOI: 10.1002/cbf.1671

A priority in recent anti‐cancer drug development has been attaining better side‐effect profiles for potential compounds. To produce highly specific cancer therapies it is necessary to understand both the effects of the proposed compound on cancer and on normal cells comprising the rest of the human body. Thus in vitro evaluation of these compounds against non‐carcinogenic cell lines is of critical importance. One of the most recent developments in experimental anti‐cancer agents is 2‐methoxyestradiol‐bis‐sulphamate (2ME‐BM), a sulphamoylated derivative of 2‐methoxyestradiol. The aim of this study was to evaluate the in vitro effects of 2ME‐BM on cell proliferation, morphology and mechanisms of cell death in the non‐carcinogenic MCF‐12A breast epithelial cell line. The study revealed changes in proliferative capacity, morphology and cell death induction in response to 2ME‐BM exposure (24 h at 0.4 µM). Microscopy showed decreased cell density and cell death‐associated morphology (increased apoptotic characteristics), a slight increase in acidic intracellular vesicles and insignificant ultra‐structural aberrations. Mitotic indices revealed a G2M‐phase cell cycle block. This was confirmed by flow cytometry, where an increased fraction of abnormal cells and a decrease in cyclin B1 levels were observed. These results evidently demonstrate that the non‐carcinogenic MCF‐12A cell line is less susceptible when compared to 2ME‐BM‐exposed cancer cell lines previously tested. Further in vitro research into the mechanism of this potentially useful compound is warranted. Copyright © 2010 John Wiley & Sons, Ltd.