N-乙酰基-硒代蛋氨酸(NASeLM),硒化合物的代表,在临床研究和细胞培养中未能说服它既不抑制癌症生长也没有化学保护作用。这项研究旨在找出NASeLM在两种不同的癌细胞上与载体物质N-乙酰基-L-蛋氨酸(NALM)相比是否显示出生长抑制特性,即Jurkat小区和MTC-SK小区。
方法:在不存在或存在不同浓度(0-500µg/mL)的NASeLM和NALM溶液的情况下培养Jurkat和MTC-SK细胞。在0、24、48和72小时后,线粒体活性,癌细胞膜CP水平,细胞生长,在Jurkat和MTC-SK细胞的等分试样中评估caspase-3活性。
结果:两种物质,纳塞姆和NALM,同样能够以浓度依赖性和时间依赖性方式抑制Jurkat细胞的细胞生长和线粒体活性达70%。只有胱天蛋白酶活性的测定显示,与对照以及同样缺乏NALM相比,只有NASeLM能够将其增加到几乎40%。然而,在MTC-SK细胞上的实验显示出与NALM相比对NASeLM有利的明显差异。虽然NASeLM能够将细胞生长降低到55%,相同数量的NALM仅在15%左右,结果证明是非常显著的(p<0.001)。对于MTC-SK线粒体活性的降低也可以测量同样的结果。也可以认识到时间依赖性:两种物质的时间越长,纳塞姆和NALM,被孵化,对细胞生长和线粒体活性的影响越高,赞成纳塞姆。只有NASeLM能够增加MTC-SK细胞中的caspase-3活性:在250µg/mL的NASeLM,与对照(14%)或相同的NALM浓度(14%)相比,caspase-3活性在24和48小时后显著增加至28%。72小时后,这仍可能增加到37%。NASeLM浓度的进一步增加没有导致更高的半胱天冬酶-3活性。
结论:NASeLM可以明显增加两种细胞类型的caspase-3活性,Jurkat或MTC-SK细胞,从而诱导细胞死亡。NALM和NASeLM显示两种细胞系的细胞生长和线粒体活性降低:而NALM和NASeLM在Jurkat细胞上显示几乎相同的测量值,NASeLM在MTC-SK上比不含硒的载体有效得多,表明它具有额外的抗化学保护作用。
N-acetyl-selenomethionine (NASeLM), a representative of the selenium compounds, failed to convince in clinical studies and cell cultures that it neither inhibits cancer growth nor has a chemoprotective effect. This study aims to find out whether NASeLM shows a growth-inhibiting property compared to the carrier substance N-Acetyl-L-methionine (NALM) on two different cancer cells, namely Jurkat cells and MTC-SK cells.
METHODS: Jurkat and MTC-SK cells were cultured in the absence or presence of varying concentrations (0-500 µg/mL) of NASeLM and NALM solutions. After 0, 24, 48, and 72 h, mitochondrial activity, cancer cell membrane CP levels, cell growth, and caspase-3 activity were assessed in aliquots of Jurkat and MTC-SK cells.
RESULTS: Both substances, NASeLM and NALM, were similarly able to inhibit cell growth and mitochondrial activity of Jurkat cells in a concentration-dependent and time-dependent manner up to 70%. Only the determination of caspase activity showed that only NASeLM was able to increase this to almost 40% compared to the control as well as the same lack of NALM. However, the experiments on MTC-SK cells showed a clear difference in favor of NASeLM compared to NALM. While NASeLM was able to reduce cell growth to up to 55%, the same amount of NALM was only at around 15%, which turned out to be highly significant (p < 0.001). The same could also be measured for the reduction in MTC-SK mitochondrial activity. Time dependence could also be recognized: the longer both substances, NASeLM and NALM, were incubated, the higher the effect on cell growth and mitochondrial activity, in favour of NASeLM. Only NASeLM was able to increase caspase-3 activity in MTC-SK cells: at 250 µg/mL NASeLM, caspase-3 activity increased significantly to 28% after 24 and 48 h compared to the control (14%) or the same NALM concentration (14%). After 72 h, this could still increase to 37%. A further increase in the NASeLM concentration did not result in higher caspase-3 activity.
CONCLUSIONS: NASeLM could clearly increase caspase-3 activity in both cell types, Jurkat or MTC-SK cells, and thus induce cell death. NALM and NASeLM showed a reduction in cell growth and mitochondrial activity in both cell lines: While NALM and NASeLM showed almost identical measurements on Jurkat cells, NASeLM was much more effective on MTC-SK than the non-selenium-containing carrier, indicating that it has additional anti-chemoprotective effects.