Diallyl disulfide induces apoptosis and autophagy via mTOR pathway in myeloid leukemic cell line
Diallyl disulfide induces apoptosis and autophagy via mTOR pathway in myeloid leukemic cell line
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DOI：
10.1007/s13277-016-4989-y
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发表时间：
2016-08-01
期刊：
影响因子：
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通讯作者：
Tanyong, Dalina I.
中科院分区：
文献类型：
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作者：
Suangtamai, Tanitta;Tanyong, Dalina I.
白血病是一种血液恶性肿瘤，由白细胞前体细胞增殖不受控制而产生。目前，已经开发出使用草药提取物的替代药物用于癌症治疗。在本研究中，研究了二烯丙基二硫化物 (DADS) 对 K562 和 NB4 髓系白血病细胞凋亡和自噬诱导的影响。用不同浓度的DADS处理白血病细胞24和48小时。使用MTT测定法测量细胞活力的百分比。通过分别用膜联蛋白-FITC 和抗 LC3 FITC 缀合抗体染色来分析细胞凋亡和自噬的百分比。然后，通过流式细胞术检测染色的细胞。此外，PP242（一种哺乳动物靶点雷帕霉素（mTOR）抑制剂）用于研究 mTOR 通路在 DADS 诱导的细胞凋亡和自噬中的作用。通过实时 PCR 测量 mTOR mRNA 表达。结果表明，DADS 以剂量和时间依赖性方式降低细胞活力并增加细胞凋亡百分比。在 DADS 和 mTOR 抑制剂处理的细胞中，mTOR 表达显着降低。在用100μg/ml DADS与10μM mTOR抑制剂联合处理的细胞中显示最高百分比的凋亡和自噬。根据我们的结果，DADS 可以通过 mTOR 途径诱导 K562 和 NB4 髓系白血病细胞系凋亡和自噬。
Leukemia is a hematological malignancy which is produced by uncontrolled proliferation of leukocyte precursors. Currently, alternative medicines, using herb extracts, have been developed for cancer treatment. In this study, the effect of diallyl disulfide (DADS) on the induction of apoptosis and autophagy was investigated in K562 and NB4 myeloid leukemia cells. Leukemia cells were treated with various concentrations of DADS for 24 and 48 h. The percentage of cell viability was measured using an MTT assay. The percentages of apoptosis and autophagy were analyzed by staining with annexin-FITC and anti-LC3 FITC-conjugated antibodies, respectively. Then, the stained cells were detected by flow cytometry. In addition, PP242, a mammalian target rapamycin (mTOR) inhibitor, was used to study the involvement of the mTOR pathway in DADS-induced apoptosis and autophagy. mTOR mRNA expression was measured by real-time PCR. The results showed that DADS decreased cell viability and increased the percentage of cell apoptosis in a dose- and time-dependent manner. mTOR expression was significantly decreased in DADS- and mTOR inhibitor-treated cells. The highest percentages of apoptosis and autophagy were shown in cells treated with 100 mu g/ml DADS combined with 10 mu M of the mTOR inhibitor. According to our results, DADS could induce apoptosis and autophagy via the mTOR pathway in both K562 and NB4 myeloid leukemia cell lines.