Department of Medical Biology, Faculty of Medicine, Altinbas University, Istanbul, Turkey.
Department of Biochemistry, Faculty of Pharmacy, Ankara University, Ankara, Turkey.
Fundam Clin Pharmacol. 2024 Dec;38(6):1094-1102. doi: 10.1111/fcp.13030. Epub 2024 Aug 8.
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.
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.
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.
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).
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.
急性髓细胞白血病（AML）在生物学和临床概念上都是一种异质性疾病。人们投入了大量精力来发现抗癌天然化合物，这些化合物在癌症治疗中显示出了巨大的潜力。甲基磺酰甲烷（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 在多种癌症中具有抗肿瘤活性。
MSM 抗白血病活性的作用机制尚不清楚。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，重点研究潜在的细胞死亡机制。
采用 MTT 法、Annexin V-PE/7AAD 染色法、caspase3/7 活性检测法和实时 qPCR 法检测 MSM 的抗癌活性。将两种细胞系分别用不同浓度（50-400mM）的 MSM 处理 24 小时。用 caspase 抑制剂（即 Z-VAD-fmk）预处理细胞，以评估细胞凋亡的诱导。
MTT 法结果表明，与对照组细胞相比，两种细胞系中 MSM 均显著降低了细胞活力。此外，Annexin V-7AAD 染色结果表明，MSM 可在两种细胞系中明显诱导细胞凋亡并激活 caspase 3/7。实时定量 PCR 结果也支持 AML 细胞中凋亡的诱导。MSM 改变了各种凋亡基因（BAX、BAD 和 BIM）的表达水平。
总的来说，我们的结果表明，MSM 可以诱导 AML 细胞系以剂量依赖的方式凋亡，因此可以用作抗白血病药物。
