芝麻素磷酸化蛋白通过诱导核抗原h731和clip相关蛋白2亚型X25介导的细胞凋亡的抗白血病活性

Pattharin Wannapruk, Atchara Paemanee, S. Roytrakul, Dalina Tanyong
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引用次数: 1

摘要

白血病是一种不受控制的造血癌细胞增殖,通常用化疗等传统疗法进行治疗。然而,据报道有许多副作用。替代药物是利用天然或草药化合物作为治疗药物而发展起来的。芝麻素是一类从芝麻中分离出来的植物雌激素,在体外和体内均表现出较强的抗癌活性,但其对白血病细胞的抗癌作用机制尚不清楚。本研究分别采用MTT法、流式细胞术、固定化金属亲和层析(IMAC)法、LC-MS法研究芝麻素对Molt-4和NB4白血病细胞株细胞活力、细胞凋亡和磷酸化蛋白表达的影响。结果表明,芝麻素降低白血病细胞活力,诱导细胞凋亡。此外,从LC-MS中鉴定出79个磷酸化蛋白,主要分布在生物调控、细胞过程和代谢过程三个主要集群中。有趣的是,核抗原H731 (PDCD4)和clip相关蛋白2异构体X25 (CLASP2)在芝麻素处理的细胞中表现出增加,并与大蒜素、辣椒素、葫芦素B和雷帕霉素等激活癌细胞凋亡的蛋白-配体相互作用网络。因此,芝麻素可以作为未来替代白血病治疗的候选药物。
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Anti-leukemic activity of phosphoproteins from Sesamin via induction of nuclear antigen H731and CLIP-associating protein 2 isoform X25 mediated apoptosis
Leukemia is an uncontrolled proliferation hematopoietic cancer cells that commonly treats with conventional therapies such as chemotherapy. However, many side effects were reported. Alternative medicines have been developed by using natural or herb compounds as therapeutic drug. Sesamin, a class of phytoestrogen isolated from sesame seed displaying potent anticancer activity in vitro and in vivo .However, the mechanism by which sesamin mediates anticancer effects on leukemic cells are notfully understood. In thisstudy, the effects of sesamin on cell viability, cell apoptosis and expression of phosphoproteins in Molt-4 and NB4 leukemic cell lines were investigated using MTT assay, flow cytometry and immobilized metal affinity chromatography (IMAC) phosphoprotein enrichment and LC-MS, respectively. The results showed that sesamin reduced viability and induced apoptosis in leukemic cells. In addition, 79 phosphoproteins were identified from LC-MS within three main clusters including biological regulation, cellular processand metabolic process. Interestingly, nuclear antigen H731 (PDCD4) and CLIP-associating protein 2 isoform X25 (CLASP2) showed increased in sesamin treated cells and associated protein-ligand interaction network with allicin, capsaicin, cucurbitacin B, and rapamycin which are known to activate apoptosis in cancer cells .Then, sesamin could be developed as candidate of alternative leukemia treatment  in the future.
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