Department of Medical Microbiology, Albert Szent-Györgyi Health Center and Albert Szent-Györgyi Medical School, University of Szeged, Szeged, Hungary.
Institute of Pharmacognosy, Faculty of Pharmacy, University of Szeged, Szeged, Hungary.
Anticancer Res. 2023 Nov;43(11):4865-4872. doi: 10.21873/anticanres.16683.
BACKGROUND/AIM: Previously, selenocompounds (Se-compounds) and in particular selenoesters have shown promising anticancer activities. Since molecular symmetry can enhance the anticancer activity, nine symmetrical selenoesters (Se-esters) have been designed as novel, potentially active anticancer agents against doxorubicin resistant breast cancer cells.
To assess the biological effects of the symmetrical Se-esters, the antiproliferative activity was determined on sensitive MCF-7 and doxorubicin resistant KCR breast cancer cell lines. The interaction of the derivatives with doxorubicin was evaluated by checkerboard combination assay on KCR cells. Furthermore, apoptosis induction and ATPase activity in the presence of Se-esters were also determined on KCR cells.
The symmetrical derivatives showed a noteworthy antiproliferative activity, with two of them showing IC values in submicromolar concentration on MCF-7 cells. In addition, some derivatives showed selectivity towards the resistant KCR cells. The combination of most of them with doxorubicin resulted in synergistic interaction, and all Se-esters could induce early and late apoptosis in KCR cells. Finally, the compounds affected the ATPase activity of ABCB1 (P-gp).
The symmetrical Se-esters showed potent anticancer activity, according to in vitro tests. Further research needs to be performed to obtain similar derivatives with a better activity and selectivity, and to ascertain the potential application of these Se-containing compounds using in vivo systems.
背景/目的：先前，硒化合物（Se-compounds），特别是硒酯，已经显示出有希望的抗癌活性。由于分子对称性可以增强抗癌活性，因此设计了九种对称硒酯（Se-esters）作为新型的、潜在的针对多柔比星耐药乳腺癌细胞的抗癌药物。
为了评估对称硒酯的生物学效应，在敏感的 MCF-7 和多柔比星耐药的 KCR 乳腺癌细胞系上测定了它们的增殖抑制活性。通过棋盘组合试验评估了衍生物与多柔比星在 KCR 细胞上的相互作用。此外，还在 KCR 细胞上测定了硒酯存在时诱导凋亡和 ATP 酶活性的情况。
对称衍生物显示出显著的增殖抑制活性，其中两种在 MCF-7 细胞上的 IC 值达到亚微摩尔浓度。此外，一些衍生物对耐药的 KCR 细胞具有选择性。它们中的大多数与多柔比星联合使用时表现出协同作用，所有硒酯都能诱导 KCR 细胞发生早期和晚期凋亡。最后，这些化合物影响了 ABCB1（P-gp）的 ATP 酶活性。
根据体外试验，对称硒酯显示出强大的抗癌活性。需要进一步研究以获得具有更好活性和选择性的类似衍生物，并利用体内系统确定这些含硒化合物的潜在应用。
