Properties of a non-bioactive fluorescent derivative of differentiation-inducing factor-3, an anti-tumor agent found in Dictyostelium discoideum.
Properties of a non-bioactive fluorescent derivative of differentiation-inducing factor-3, an anti-tumor agent found in Dictyostelium discoideum.
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DOI：
10.1242/bio.20146585
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发表时间：
2014-04-15
期刊：
影响因子：
2.4
通讯作者：
Homma Y
中科院分区：
文献类型：
--
作者：
Kubohara Y;Kikuchi H;Matsuo Y;Oshima Y;Homma Y
分化诱导因子-3（DIF-3），发现于细胞黏菌盘基网柄菌（Dictyosteoproteindiscoideum）中，及其衍生物，如丁氧基-DIF-3（Bu-DIF-3），是有效的抗肿瘤剂。为了研究DIF样分子在肿瘤细胞中的活性，我们合成了一种绿色荧光DIF-3衍生物BODIPY-DIF-3G，并对其生物活性和细胞定位进行了分析。本研究合成了一种红色（橙子色）荧光DIF-3衍生物BODIPY-DIF-3R，并比较了两种BODIPY-DIF-3在HeLa人宫颈癌细胞中的细胞定位和生物活性。两种荧光化合物均在0.5小时内穿透细胞外膜，并主要定位于线粒体。 在福尔马林固定的细胞中，两个BODIPY-DIF-3也定位于线粒体，表明BODIPY-DIF-3独立于线粒体膜电位被掺入线粒体。处理3天后，BODIPY-DIF-3G而不是BODIPY-DIF-3R诱导线粒体肿胀并抑制细胞增殖。有趣的是，肿胀的线粒体被BODIPY-DIF-3G包裹，而不是被BODIPY-DIF-3R包裹。当加入到离体线粒体中时，BODIPY-DIF-3G剂量依赖性地增加O2消耗速率，但BODIPY-DIF-3R没有。这些结果表明，生物活性BODIPY-DIF-3G通过改变线粒体活性至少部分地抑制细胞增殖，而非生物活性BODIPY-DIF-3R定位于线粒体但不影响线粒体活性或细胞增殖。
Differentiation-inducing factor-3 (DIF-3), found in the cellular slime mold Dictyostelium discoideum, and its derivatives, such as butoxy-DIF-3 (Bu-DIF-3), are potent anti-tumor agents. To investigate the activity of DIF-like molecules in tumor cells, we recently synthesized a green fluorescent DIF-3 derivative, BODIPY-DIF-3G, and analyzed its bioactivity and cellular localization. In this study, we synthesized a red (orange) fluorescent DIF-3 derivative, BODIPY-DIF-3R, and compared the cellular localization and bioactivities of the two BODIPY-DIF-3s in HeLa human cervical cancer cells. Both fluorescent compounds penetrated the extracellular membrane within 0.5 h and localized mainly to the mitochondria. In formalin-fixed cells, the two BODIPY-DIF-3s also localized to the mitochondria, indicating that the BODIPY-DIF-3s were incorporated into mitochondria independently of the mitochondrial membrane potential. After treatment for 3 days, BODIPY-DIF-3G, but not BODIPY-DIF-3R, induced mitochondrial swelling and suppressed cell proliferation. Interestingly, the swollen mitochondria were stainable with BODIPY-DIF-3G but not with BODIPY-DIF-3R. When added to isolated mitochondria in vitro, BODIPY-DIF-3G increased dose-dependently the rate of O2 consumption, but BODIPY-DIF-3R did not. These results suggest that the bioactive BODIPY-DIF-3G suppresses cell proliferation, at least in part, by altering mitochondrial activity, whereas the non-bioactive BODIPY-DIF-3R localizes to the mitochondria but does not affect mitochondrial activity or cell proliferation.
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DOI：
10.1126/science.1164551
发表时间：
2009-02-06
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Wegrzyn J;Potla R;Chwae YJ;Sepuri NB;Zhang Q;Koeck T;Derecka M;Szczepanek K;Szelag M;Gornicka A;Moh A;Moghaddas S;Chen Q;Bobbili S;Cichy J;Dulak J;Baker DP;Wolfman A;Stuehr D;Hassan MO;Fu XY;Avadhani N;Drake JI;Fawcett P;Lesnefsky EJ;Larner AC
通讯作者：
Larner AC
影响因子：
5.5
作者：
Kabuyama, Yukihito;Suzuki, Toshiyuki;Homma, Yoshimi
通讯作者：
Homma, Yoshimi
影响因子：
4.1
作者：
MORRIS, HR;MASENTO, MS;KAY, RR
通讯作者：
KAY, RR
DOI：
10.1006/bbrc.1997.6964
发表时间：
1997-07-18
影响因子：
3.1
作者：
Kubohara, Y
通讯作者：
Kubohara, Y
影响因子：
6.1
作者：
Kikuchi, Haruhisa;Oshima, Yoshiteru;Kubohara, Yuzuru
通讯作者：
Kubohara, Yuzuru