Institute of Medical Microbiology and Immunobiology, Faculty of Medicine, University of Szeged, Dóm tér 10, H-6720 Szeged, Hungary.
Anticancer Res. 2011 Oct;31(10):3285-8.
Hydantoin derivatives are very promising candidates to improve the efficacy of anticancer chemotherapy. Previously, we demonstrated that eight hydantoin derivatives inhibited the P-glycoprotein (ABCB1) efflux pump of mouse T-lymphoma cells, as well as acting synergistically with the anticancer drug doxorubicin.
The activity of the hydantoin derivatives were investigated in another MDR cancer model, namely Colo 205/S sensitive and Colo 320/R resistant colon carcinoma cells respectively, having normal or overexpressed ABCB1 systems.
Among the hydantoin derivatives evaluated, BS-1, MN-3 and JH-63 were the most effective ABCB1 transporter inhibitors at the concentration of 4 mg/l on the Colo 320/R cells, compared to the positive control, verapamil.
The derivatives did not induce apoptosis of Colo 320/R resistant colon carcinoma cells, indicating that these hydantoin compounds are potent efflux pump inhibitors (EPI) without affecting the signalling pathways that regulate apoptosis.
海因衍生物是提高癌症化疗疗效的很有前途的候选物。以前，我们证明了八种海因衍生物抑制了小鼠 T 淋巴细胞瘤细胞的 P-糖蛋白（ABCB1）外排泵，并且与抗癌药物阿霉素具有协同作用。
在另一个 MDR 癌症模型中，即 Colo 205/S 敏感和 Colo 320/R 耐药结肠癌细胞中，研究了海因衍生物的活性，这些细胞分别具有正常或过表达的 ABCB1 系统。
在所评估的海因衍生物中，BS-1、MN-3 和 JH-63 在 4 mg/l 浓度下对 Colo 320/R 细胞是最有效的 ABCB1 转运蛋白抑制剂，与阳性对照维拉帕米相当。
这些衍生物不会诱导 Colo 320/R 耐药结肠癌细胞凋亡，表明这些海因化合物是有效的外排泵抑制剂（EPI），而不影响调节细胞凋亡的信号通路。
