Institute of Immunology, Faculty of Medicine, Comenius University, Odborarske nam. 14, 811 08, Bratislava, Slovak Republic.
Biomedical Research Center, Cancer Research Institute, Slovak Academy of Sciences, Dubravska cesta 9, 845 05, Bratislava, Slovak Republic.
Med Oncol. 2022 May 23;39(5):99. doi: 10.1007/s12032-022-01692-1.
Intensive investigation for novel antiproliferative and cytotoxic effective chemical compounds is currently concentrated on structurally modified agents of natural or synthetic source. The selenium derivative of triorganotin compound, triphenyltin isoselenocyanate (TPT-NCSe) caused higher cytotoxicity in hormone sensitive MCF 7 (IC 50-250 nM) in comparison with triple-negative MDA-MB-231 breast carcinoma cell line (IC 50-450 nM) as determined by MTT assay. Measurement of DNA damage showed presence of crosslinks in both cell lines treated by increasing TPT-NCSe concentrations. This compound decreased mitochondrial membrane potential shown by JC-1 staining in a concentration-dependent manner in both cell lines. Activation of caspases-3/7 was observed in MDA-MB-231 cells and was significant only by concentrations causing significant level of crosslinks. On the other hand, migration assay revealed inhibitory effect of viability keeping 100 nM concentration of TPT-NCSe on migration of MDA-MB-231 cells. Our data has shown that this selenium containing triorganotin molecule exerts DNA damage-linked antineoplastic activity in breast carcinoma cell lines studied.
目前，人们集中精力对天然或合成来源的结构修饰剂进行深入研究，以寻找具有新型抗增殖和细胞毒性作用的化学化合物。三丁基锡化合物的硒衍生物三苯基锡异硒氰酸酯（TPT-NCSe）在 MTT 测定中对激素敏感的 MCF 7（IC 50-250 nM）细胞系比三阴性 MDA-MB-231 乳腺癌细胞系（IC 50-450 nM）表现出更高的细胞毒性。DNA 损伤的测量表明，在用 TPT-NCSe 浓度增加处理的两种细胞系中均存在交联。该化合物以浓度依赖的方式降低了 JC-1 染色显示的两种细胞系中线粒体膜电位。在 MDA-MB-231 细胞中观察到 caspase-3/7 的激活，并且仅在导致交联水平显著增加的浓度下才具有统计学意义。另一方面，迁移实验表明，在保持 100 nM TPT-NCSe 浓度的情况下，对 MDA-MB-231 细胞的迁移具有抑制作用。我们的数据表明，这种含有硒的三丁基锡分子在研究的乳腺癌细胞系中表现出与 DNA 损伤相关的抗肿瘤活性。
