In vitro effects of 2-methoxyestradiol on canine tumour cells |
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Authors: | A K Marr D H Thamm I D Kurzman D M Vail E G MacEwen |
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Institution: | Department of Medical Sciences, School of Veterinary Medicine, University of Wisconsin, Madison, WI, USA;The Comprehensive Cancer Center, University of Wisconsin, Madison, WI, USA |
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Abstract: | The in vitro antiproliferative, apoptotic and cell‐cycle effects of 2‐methoxyestradiol (2ME2), an endogenous oestrogen metabolite, were investigated using a variety of canine tumour cell lines. The cells were cultured under standard conditions and incubated with varying concentrations of 2ME2. Inhibition of tumour cell proliferation was evaluated using a tetrazolium‐based colorimetric assay. DNA content analysis was performed using propidium iodide staining and flow cytometry. Cytologic analysis with Leukostat staining solution and Hoechst 33342 staining and Annexin V‐fluorescein isothiocyanate (FITC) fluorescence were used to quantify cell‐cycle distribution and apoptosis induction. Tumour cell proliferation was inhibited by 50% at concentrations of 2ME2 ranging from 0.88 to 7.67 µM, depending on the cell line tested. Profound G2/M phase arrest, an increase in binucleate cells and induction of apoptosis were observed in all cell lines tested, in a dose‐dependent manner. Based on these results, this compound has potential as an agent for the treatment of canine cancer and warrants further investigation. The canine lymphoma cell line, 1771, was inhibited at concentrations that may be achievable in vivo. |
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Keywords: | apoptosis cancer cell cycle dog oestrogen proliferation tissue culture |
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