Hunakova Luba, Brtko Julius
Cancer Research Institute, BMC, Slovak Academy of Sciences, Dubravska cesta 9, 845 05 Bratislava, Slovak Republic.
Institute of Experimental Endocrinology, BMC, Slovak Academy of Sciences, Dubravska cesta 9, 845 05 Bratislava, Slovak Republic.
Toxicol Lett. 2017 Sep 5;279:16-21. doi: 10.1016/j.toxlet.2017.07.879. Epub 2017 Jul 12.
Among a variety of metal containing organic compounds, tin derivatives are enjoying an increasing interest and appear to be very promising as potential drug candidates. We studied eight organometallic derivatives, nuclear retinoid X receptor (RXR) ligands and two germanium containing derivates that do not serve as RXR ligands. Tributylgermanium chloride (TBGe) and triphenylgermanium chloride (TPGe) did not inhibit growth of human triple negative MDA-MB-231 breast cancer cells. On the other hand, the tributyltin derivatives were highly, the triphenyltin derivatives less cytotoxic, both groups with IC values of nanomolar range. All trialkyltin derivatives (tributyltin chloride, tributyltin bromide, tributyltin iodide, tributyltin hydride) and three triaryltin derivatives (triphenyltin chloride, triphenyltin hydride and triphenyltin hydroxide) caused caspase-3/7 dependent apoptosis. Those derivatives that showed no or weak cytotoxicity, TBGe, TPGe, and triphenyltin acetate, we found to reduce migration of tested triple negative breast cancer cells.
在各种含金属有机化合物中，锡衍生物越来越受到关注，并且作为潜在的药物候选物似乎非常有前景。我们研究了八种有机金属衍生物、核视黄酸X受体（RXR）配体以及两种不作为RXR配体的含锗衍生物。三丁基氯化锗（TBGe）和三苯基氯化锗（TPGe）不抑制人三阴性MDA-MB-231乳腺癌细胞的生长。另一方面，三丁基锡衍生物具有高度细胞毒性，三苯基锡衍生物细胞毒性较小，两组的半数抑制浓度（IC）值均在纳摩尔范围内。所有三烷基锡衍生物（三丁基氯化锡、三丁基溴化锡、三丁基碘化锡、三丁基氢化锡）和三种三芳基锡衍生物（三苯基氯化锡、三苯基氢化锡和三苯基氢氧化锡）均引起半胱天冬酶-3/7依赖性凋亡。我们发现，那些没有或只有微弱细胞毒性的衍生物，即TBGe、TPGe和三苯基乙酸锡，可减少受试三阴性乳腺癌细胞的迁移。
