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KMID : 0613820140240020173
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Journal of Life Science
2014 Volume.24 No. 2 p.173 ~ p.180
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Fulvestrant Does Not Have Antagonistic Effect on 17β-estradiol's Anti-proliferative Action in Cultured Chinese Hamster Ovarian Cell Line
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Kim Hyun-Hee
Park Hyeong-Cheol
Min Gye-sik
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Abstract
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Estrogen can promote or inhibit cellular proliferation depending on tissue cell types and physiological condition and acts through the signal transduction pathways mediated primarily by estrogen receptors. This study examined the effects of fulvestrant (Ful), a well-known antagonist for the estrogen receptor, on the action of 17β-estradiol (E2) with respect to the proliferation and apoptosis of Chinese hamster ovarian (CHO) cells. We used different concentrations of E2, Ful, and E2 plus Ful during different treatment durations. Treatment with 15-40 μM E2 significantly inhibited proliferation in a time-dependent manner, although it had no influence in concentrations up to 1 μM. Interestingly, Ful at 10-40 μM also inhibited cellular proliferation in both a concentration- and time-dependent manner. In addition, Ful enhanced rather than decreased the inhibitory effect on cellular proliferation by E2 in combined treatment for 10 days. Thus, Ful does not appear to have an antagonistic effect on estrogen's anti-proliferative action in CHO cells. In TUNEL assays to confirm DNA fragmentation by E2 and/or Ful, CHO cells treated with 20 μM E2 showed a TUNEL-positive reaction in most DAPI-stained nuclei, and cells treated with either 40 μM Ful or 40 μM Ful plus 20 μM E2 also exhibited a TUNEL-positive reaction but at a lower rate compared to the E2-treated cells. These results indicate that Ful does not have an antagonistic effect on estrogen's anti-proliferative action in CHO cells, suggesting that the anti-proliferative and apoptosis-related mechanism(s) through DNA fragmentation by E2 and Ful may be mediated by different signal transduction pathways.
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KEYWORD
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17β-estradiol (E2), Chinese hamster ovarian (CHO), DNA fragmentation, fulvestrant, proliferation
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