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首页> 外文期刊>Cell cycle >Salarin C inhibits the maintenance of chronic myeloid leukemia progenitor cells
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Salarin C inhibits the maintenance of chronic myeloid leukemia progenitor cells

机译：Salarin C抑制慢性粒细胞白血病祖细胞的维持

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摘要

We previously showed that incubation of chronic myeloid leukemia (CML) cells in very low oxygen selects a cell subset where the oncogenetic BCR/Abl protein is suppressed and which is thereby refractory to tyrosine kinase inhibitors used for CML therapy. In this study, salarin C, an anticancer macrolide extracted from the Fascaplysinopsis sponge, was tested as for its activity on CML cells, especially after their incubation in atmosphere at 0.1% oxygen. Salarin C induced mitotic cycle arrest, apoptosis and DNA damage. Salarin C also concentration-dependently inhibited the maintenance of stem cell potential in cultures in low oxygen of either CML cell lines or primary cells. Surprisingly, the drug also concentration-dependently enforced the maintenance of BCR/Abl signaling in low oxygen, an effect which was paralleled by the rescue of sensitivity of stem cell potential to IM. These results suggest a potential use of salarin C for the suppression of CML cells refractory to tyrosine kinase inhibitors
机译：我们先前显示，慢性骨髓性白血病（CML）细胞在极低的氧气中孵育会选择一种细胞子集，其中致癌基因BCR / Abl蛋白被抑制，因此对于CML治疗中使用的酪氨酸激酶抑制剂是难治的。在这项研究中，对Salarin C（一种从Fascaplysinopsis海绵中提取的抗癌大环内酯类化合物）对CML细胞的活性进行了测试，尤其是在0.1％氧气中在大气中孵育后。 Salarin C诱导有丝分裂周期停滞，凋亡和DNA损伤。 Salarin C还浓度依赖性地抑制了CML细胞系或原代细胞低氧培养物中干细胞电位的维持。出人意料的是，该药物还以浓度依赖性地在低氧下维持了BCR / Abl信号的维持，这一作用与拯救干细胞对IM的敏感性相平行。这些结果表明，Salarin C可能用于抑制酪氨酸激酶抑制剂难治的CML细胞

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