Division of Medicinal Chemistry, Otto Loewi Research, Medical University of Graz, 8010 Graz, Austria.
Division of Transplantation Surgery, Medical University of Graz, 8010 Graz, Austria.
Cells. 2024 May 29;13(11):937. doi: 10.3390/cells13110937.
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.
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.
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 ( < 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.
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.
研究 N-乙酰-L-硒蛋氨酸（NASeLM）与载体物质 N-乙酰-L-蛋氨酸（NALM）相比，是否对两种不同的癌细胞（即 Jurkat 细胞和 MTC-SK 细胞）具有生长抑制作用。
在无或存在不同浓度（0-500μg/ml）NASeLM 和 NALM 溶液的情况下培养 Jurkat 和 MTC-SK 细胞。在 0、24、48 和 72 h 后，评估 Jurkat 和 MTC-SK 细胞中线粒体活性、癌细胞膜 CP 水平、细胞生长和 caspase-3 活性。
NASeLM 和 NALM 均能以浓度和时间依赖性方式抑制 Jurkat 细胞的生长和线粒体活性，抑制率高达 70%。只有 caspase 活性的测定表明，与对照组相比，只有 NASeLM 能够将其提高近 40%，而 NALM 则没有。然而，在 MTC-SK 细胞的实验中，NASeLM 与 NALM 相比表现出明显的差异。虽然 NASeLM 能够将细胞生长降低至 55%，但相同浓度的 NALM 仅为 15%，这具有显著差异（<0.001）。在 MTC-SK 线粒体活性的降低方面也可以观察到同样的情况。时间依赖性也可以识别：NASeLM 和 NALM 孵育时间越长，对细胞生长和线粒体活性的影响就越高，对 NASeLM 有利。只有 NASeLM 能够增加 MTC-SK 细胞中的 caspase-3 活性：在 250μg/ml NASeLM 下，与对照组（14%）或相同浓度的 NALM（14%）相比，caspase-3 活性在 24 和 48 h 时显著增加至 28%。72 h 后，仍可增加至 37%。NASeLM 浓度的进一步增加不会导致 caspase-3 活性的增加。
NASeLM 可以明显增加两种细胞类型（Jurkat 或 MTC-SK 细胞）中的 caspase-3 活性，从而诱导细胞死亡。NALM 和 NASeLM 均降低了两种细胞系中的细胞生长和线粒体活性：虽然 NALM 和 NASeLM 在 Jurkat 细胞上的测量结果几乎相同，但 NASeLM 对 MTC-SK 的效果比不含硒的载体物质 NALM 更为显著，表明其具有额外的抗化学保护作用。
