Abstract:
There is some evidence that non-photoactivated psoralens may be active against breast and colon tumor cells. Therefore, we evaluated the antiproliferative, proapoptotic, and anti-migrative effect of 5-methoxypsoralen (5-MOP) isolated from Peucedanum tauricum MB fruits in human colorectal adenocarcinoma (HT-29 and SW620), osteosarcoma (Saos-2 and HOS), and multiple myeloma (RPMI8226 and U266). Dose- and cell-line-dependent effects of 5-MOP on viability and proliferation were observed, with the strongest inhibitory effect against Saos-2 and a moderate effect against the HOS, HT-29, and SW620 cells. Multiple myeloma showed low sensitivity. The high viability of human normal cell cultures (HSF and hFOB) in a wide range of 5-MOP concentrations tested (6.25-100 µM) was confirmed. Moreover, the migration of treated Saos-2, SW620, and HT-29 cell lines was impaired, as indicated via a wound healing assay. Flow cytometry analysis conducted on Saos-2 cells revealed the ability of 5-MOP to block the cell cycle in the G2 phase and trigger apoptosis, which was accompanied by a loss of mitochondrial membrane potential, caspases (-9 and -3) activation, the altered expression of the Bax and Bcl-2 proteins, and decreased AKT phosphorylation. This is the first report evaluating the antiproliferative and antimigratory impact of non-UV-activated bergapten on the abovementioned (except for HT-29) tumor cells, which provides new data on the potential role of 5-MOP in inhibiting the growth of various types of therapeutic-resistant cancers.
摘要:
有一些证据表明,非光活化的补骨脂素可能对乳腺和结肠肿瘤细胞具有活性。因此,我们评估了抗增殖,促凋亡,和5-甲氧基补骨脂素(5-MOP)在人大肠腺癌(HT-29和SW620)中的抗迁移作用,骨肉瘤(Saos-2和HOS),和多发性骨髓瘤(RPMI8226和U266)。观察到5-MOP对活力和增殖的剂量和细胞系依赖性作用。对Saos-2的抑制作用最强,对HOS的抑制作用中等,HT-29和SW620细胞。多发性骨髓瘤敏感性低。证实了人类正常细胞培养物(HSF和hFOB)在测试的5-MOP浓度范围广泛(6.25-100µM)中的高生存力。此外,处理的Saos-2,SW620和HT-29细胞系的迁移受损,如通过伤口愈合试验所示。对Saos-2细胞进行的流式细胞术分析揭示了5-MOP在G2期阻断细胞周期并引发细胞凋亡的能力,伴随着线粒体膜电位的丧失,胱天蛋白酶(-9和-3)激活,Bax和Bcl-2蛋白表达的改变,并降低AKT磷酸化。这是第一份评估非紫外线激活的bergapten对上述(HT-29除外)肿瘤细胞的抗增殖和抗迁移影响的报告,这提供了有关5-MOP在抑制各种类型的治疗抗性癌症生长中的潜在作用的新数据。