背景:急性髓性白血病(AML)在生物学和临床概念上都是一种异质性疾病。已经做出了许多努力来发现用于对抗癌症的天然化合物,在癌症管理中显示出巨大的潜力。甲磺酰基甲烷(MSM),一种有机硫膳食补充剂,用于改善各种临床状况,特别是骨关节炎。MSM可以在多种癌症中发挥抗肿瘤活性。
目的:MSM抗白血病活性的分子机制尚不清楚。在这方面,我们旨在研究MSM对人AML细胞系(U937和HL60)的抗癌特性,重点是潜在的细胞死亡机制。
方法:采用MTT法检测MSM的抗癌活性,膜联蛋白V-PE/7AAD染色,caspase3/7活性测试,和实时qPCR。两种细胞系均用不同浓度(50-400mM)的MSM处理24小时。用半胱天冬酶抑制剂预处理细胞(即,Z-VAD-fmk)用于评估凋亡诱导。
结果:MTT实验结果显示,在两种细胞系中,与对照细胞相比,MSM显著降低细胞活力。此外,膜联蛋白V-7AAD染色发现,MSM在两种细胞系中均显着诱导凋亡和激活的caspase3/7。实时定量PCR结果也支持诱导AML细胞凋亡。MSM改变了各种凋亡基因的表达水平(BAX,糟糕,BIM)。
结论:总体而言,我们的结果表明,MSM可以以剂量依赖的方式诱导AML细胞系凋亡,因此可以用作抗白血病药。
BACKGROUND: Acute myeloid leukemia (AML) is a heterogeneous ailment in both biological and clinical concepts. Numerous efforts have been devoted to discover natural compounds for combating cancer, which showed great potential in cancer management. Methylsulfonylmethane (MSM), an organosulfur dietary supplement, is utilized for improving various clinical conditions, particularly osteoarthritis. MSM can exert antitumor activity in a wide range of cancers.
OBJECTIVE: The molecular mechanisms of action underlying antileukemic activity of MSM remain unclear. In this regard, we aimed to investigate the anticancer properties of MSM on human AML cell lines (U937 and HL60) with focus on underlying cell death mechanism.
METHODS: Anticancer activity of the MSM was examined employing MTT assay, Annexin V-PE/7AAD staining, caspase3/7 activity test, and real-time qPCR. Both cell lines were treated with different concentrations (50-400 mM) of MSM for 24 h. Pretreatment of the cells with a
caspase inhibitor (i.e., Z-VAD-fmk) was performed for the assessment of apoptosis induction.
RESULTS: The results of MTT assay revealed that in both cell lines, the MSM markedly reduced cell viability in comparison to the control cells. Additionally, findings of Annexin V-7AAD staining revealed that MSM induced apoptosis and activated
caspase 3/7 in both cell lines markedly. Real-time quantitative PCR results also supported the induction of apoptosis in AML cells. MSM altered the expression levels of various apoptotic genes (BAX, BAD, and BIM).
CONCLUSIONS: Overall, our results indicated that MSM could induce apoptosis in AML cell lines in a dose-dependent manner, which therefore could be utilized as an antileukemic agent.