N-乙酰-L-硒代蛋氨酸对两种产生 RONS 的癌细胞系与 N-乙酰-L-蛋氨酸的影响比较。

The Influence of N-Acetyl-selenomethionine on Two RONS-Generating Cancer Cell Lines Compared to N-Acetyl-methionine.

机构信息

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.

出版信息

Cells. 2024 May 29;13(11):937. doi: 10.3390/cells13110937.

DOI:10.3390/cells13110937

PMID:38891069

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11172027/

Abstract

UNLABELLED

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 ( < 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.

CONCLUSION

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.

摘要

目的

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。

方法

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。

结果

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。

结论

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。