The rRNA synthesis inhibitor CX-5461 may induce autophagy that inhibits anticancer drug-induced cell damage to leukemia cells
The rRNA synthesis inhibitor CX-5461 may induce autophagy that inhibits anticancer drug-induced cell damage to leukemia cells
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DOI：
10.1080/09168451.2020.1801378
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发表时间：
2020-08
期刊：
影响因子：
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通讯作者：
Shuichiro Okamoto;K. Miyano;M. Kajikawa;A. Yamauchi;F. Kuribayashi
中科院分区：
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作者：
Shuichiro Okamoto;K. Miyano;M. Kajikawa;A. Yamauchi;F. Kuribayashi
化疗期间癌细胞诱导的自噬分为两种类型，根据细胞类型或抗癌药物的不同而不同。第一种类型的自噬导致药物治疗的细胞死亡。相反，第二种类型在预防抗癌药物引起的细胞损伤中起着至关重要的作用；使用自噬抑制剂被认为能有效提高化疗的疗效。因此，确定化疗期间诱导的自噬类型是很重要的。在这里，我们发现了一种新的RNA聚合酶I抑制剂，可以抑制白血病细胞系的生长，诱导细胞周期阻滞并促进细胞凋亡。CX-5461与自噬抑制剂氯喹共同作用诱导的凋亡细胞数量比CX-5461单独作用时增加。因此，CX-5461可能诱导的自噬是第二类。CX-5461与CQ共作用诱导的凋亡细胞数量较单独作用CX-5461增加。
ABSTRACT Autophagy induced in cancer cells during chemotherapy is classified into two types, which differ depending on the kind of cells or anticancer drugs. The first type of autophagy contributes to the death of cells treated with drugs. In contrast, the second type plays a crucial role in preventing anticancer drug-induced cell damages; the use of an autophagy inhibitor is considered effective in improving the efficacy of chemotherapy. Thus, it is important to determine which type of autophagy is induced during chemotherapy. Here, we showed that a novel inhibitor of RNA polymerase I, suppresses growth, induces cell cycle arrest and promotes apoptosis in leukemia cell lines. The number of apoptotic cells induced by co-treatment with CX-5461 and chloroquine, an autophagy inhibitor, increased compared with CX-5461 alone. Thus, the autophagy which may be induced by CX-5461 was the second type. Graphical Abstract The number of apoptotic cells induced by co-treatment with CX-5461 and CQ increased compared with CX-5461 alone.