Methylsulfonylmethane induces caspase-dependent apoptosis in acute myeloid leukemia cell lines

IF 2.1 4区 医学 Q3 PHARMACOLOGY & PHARMACY
Yalda Hekmatshoar, Arzu Zeynep Karabay, Tulin Ozkan, Asli Koc, Asuman Sunguroglu
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引用次数: 0

Abstract

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. Objectives: 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). Conclusion: 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.

甲基磺酰基甲烷可诱导急性髓性白血病细胞系发生依赖于 Caspase 的细胞凋亡。
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。人们致力于发现抗癌的天然化合物,这些化合物在癌症治疗中显示出巨大的潜力。甲基磺酰基甲烷(MSM)是一种有机硫膳食补充剂,可用于改善各种临床症状,尤其是骨关节炎。MSM 可在多种癌症中发挥抗肿瘤活性:MSM 抗白血病活性的分子作用机制尚不清楚。为此,我们旨在研究 MSM 对人类急性髓细胞白血病细胞系(U937 和 HL60)的抗癌特性,并重点研究其潜在的细胞死亡机制:方法:采用 MTT 试验、Annexin V-PE/7AAD 染色、caspase3/7 活性测试和实时 qPCR 检测 MSM 的抗癌活性。用 Caspase 抑制剂(即 Z-VAD-fmk)对细胞进行预处理,以评估细胞凋亡诱导情况:MTT检测结果显示,与对照细胞相比,MSM明显降低了两种细胞系的细胞活力。此外,Annexin V-7AAD 染色结果显示,MSM 在两种细胞系中都能明显诱导细胞凋亡并激活 caspase 3/7。实时定量 PCR 结果也证实了 MSM 诱导急性髓细胞白血病细胞凋亡的作用。MSM改变了多种凋亡基因(BAX、BAD和BIM)的表达水平:总之,我们的研究结果表明,MSM 能以剂量依赖的方式诱导 AML 细胞株凋亡,因此可用作抗白血病药物。
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来源期刊
CiteScore
5.30
自引率
6.90%
发文量
111
审稿时长
6-12 weeks
期刊介绍: Fundamental & Clinical Pharmacology publishes reports describing important and novel developments in fundamental as well as clinical research relevant to drug therapy. Original articles, short communications and reviews are published on all aspects of experimental and clinical pharmacology including: Antimicrobial, Antiviral Agents Autonomic Pharmacology Cardiovascular Pharmacology Cellular Pharmacology Clinical Trials Endocrinopharmacology Gene Therapy Inflammation, Immunopharmacology Lipids, Atherosclerosis Liver and G-I Tract Pharmacology Metabolism, Pharmacokinetics Neuropharmacology Neuropsychopharmacology Oncopharmacology Pediatric Pharmacology Development Pharmacoeconomics Pharmacoepidemiology Pharmacogenetics, Pharmacogenomics Pharmacovigilance Pulmonary Pharmacology Receptors, Signal Transduction Renal Pharmacology Thrombosis and Hemostasis Toxicopharmacology Clinical research, including clinical studies and clinical trials, may cover disciplines such as pharmacokinetics, pharmacodynamics, pharmacovigilance, pharmacoepidemiology, pharmacogenomics and pharmacoeconomics. Basic research articles from fields such as physiology and molecular biology which contribute to an understanding of drug therapy are also welcomed.
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