Division of Pulmonary Medicine, Department of Internal Medicine, Wanfang Hospital, Taipei Medical University, Taipei, Taiwan.
Division of Pulmonary Medicine, Department of Internal Medicine, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan.
Pharmacology. 2018;102(5-6):262-271. doi: 10.1159/000492494. Epub 2018 Sep 18.
We previously synthesized new tubulin inhibitors, MPT0B169 and MPT0B002, which induced growth inhibition and apoptosis in leukemia cells. However, their effects on solid tumor cells have not been determined. In this study, we investigated the effects of MPT0B169 and MPT0B002 on glioblastoma, breast, lung, and colorectal cancer (CRC) cell lines. A cell viability analysis showed that MPT0B169 and MPT0B002 were more effective in inhibiting the proliferation of COLO205 and HT29 CRC cells than U87MG and GBM8401 glioblastoma, MCF-7 and MDA-MB-231 breast cancer, and A549 lung cancer cells. MPT0B169 and MPT0B002 inhibited growth of COLO205 and HT29 cells in dose- and time-dependent manners. A colony-formation assay confirmed the growth inhibitory effects of MPT0B169 and MPT0B002 on COLO205 and HT29 cells. MPT0B169 and MPT0B002 disrupted tubulin polymerization and arrested the cell cycle at the G2/M phase, with a concomitant increase of the cyclin B1 level. MPT0B169 and MPT0B002 induced apoptosis, accompanied by induction of the intrinsic apoptotic pathway, as shown by a reduction in the caspase-9 level and increases in cleaved caspase-3 and cleaved PARP. These results suggest that MPT0B169 and MPT0B002, new tubulin inhibitors, induced growth inhibition, G2/M arrest, and apoptosis in COLO205 and HT29 cells, and they could potentially be anticancer agents for CRC cells.
我们之前合成了新的微管蛋白抑制剂 MPT0B169 和 MPT0B002，它们在白血病细胞中诱导了生长抑制和细胞凋亡。然而，它们对实体肿瘤细胞的影响尚未确定。在这项研究中，我们研究了 MPT0B169 和 MPT0B002 对胶质母细胞瘤、乳腺癌、肺癌和结直肠癌（CRC）细胞系的影响。细胞活力分析表明，MPT0B169 和 MPT0B002 对 COLO205 和 HT29 CRC 细胞的增殖抑制作用比对 U87MG 和 GBM8401 胶质母细胞瘤、MCF-7 和 MDA-MB-231 乳腺癌以及 A549 肺癌细胞更为有效。MPT0B169 和 MPT0B002 以剂量和时间依赖的方式抑制 COLO205 和 HT29 细胞的生长。集落形成实验证实了 MPT0B169 和 MPT0B002 对 COLO205 和 HT29 细胞生长的抑制作用。MPT0B169 和 MPT0B002 破坏微管蛋白聚合并将细胞周期阻滞在 G2/M 期，同时细胞周期蛋白 B1 水平升高。MPT0B169 和 MPT0B002 诱导细胞凋亡，并伴有内源性凋亡途径的诱导，表现为 caspase-9 水平降低，cleaved caspase-3 和 cleaved PARP 水平升高。这些结果表明，新的微管蛋白抑制剂 MPT0B169 和 MPT0B002 诱导 COLO205 和 HT29 细胞生长抑制、G2/M 期阻滞和细胞凋亡，它们可能是 CRC 细胞的抗癌药物。
