A novel synthesized 3', 5'-diprenylated chalcone mediates the proliferation of human leukemia cells by regulating apoptosis and autophagy pathways.
A novel synthesized 3', 5'-diprenylated chalcone mediates the proliferation of human leukemia cells by regulating apoptosis and autophagy pathways.
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DOI：
10.1016/j.biopha.2018.06.153
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发表时间：
2018-10
影响因子：
7.5
通讯作者：
Luo Heng
中科院分区：
文献类型：
--
作者：
Zhang Yong-Qiang;Wen Zhong-Hang;Wan Ke;Yuan Dongbo;Zeng Xiaoping;Liang Guangyi;Zhu Jianguo;Xu Bixue;Luo Heng
白血病是一种预后较差的血液系统恶性肿瘤，化疗是白血病患者的主要治疗策略。治疗患者需要选择性更好、毒性更低的新型药物。新型3‘，5’-二戊烯基查尔酮(E)-1-(2-羟基-4-甲氧基-3，5-二戊烯基)苯基-3-(3-吡啶基)丙烯-1-酮(C10)是一种潜在的抗白血病新药。本研究探讨了C10在体外对不同白血病细胞的抗白血病作用的分子机制。C10对人红白血病细胞系HEL和人髓系白血病细胞系K562有较强的增殖抑制作用，多项细胞和流式细胞仪分析表明，C10的抑制作用是通过调节凋亡和自噬途径中的基因表达或磷酸化而实现的。结果表明，C10可在蛋白水平调控Bax、c-Myc、Bcl2、P38/AMPK和ERK1/2的表达，在蛋白水平激活Caspase-3、-8和PARP的表达，抑制人红白血病细胞系HEL中致癌基因Fli-1的表达。此外，用该化合物处理后，LC3A/B的表达呈时间依赖性增加，抑制了AKT-mTOR途径，这与细胞自噬有关。综上所述，上述结果表明，新合成的3‘，5’-二戊烯基查尔酮可以通过诱导细胞凋亡和自噬来抑制白血病细胞的生长。
Leukemia is a hematologic malignancy with poor prognosis in humans and chemotherapy is the main strategy for treating leukemia patients. Novel drugs with better selectivity and lower toxicity are required for the treatment of patients. A novel 3’,5’-diprenylated chalcone, (E)-1-(2-hydroxy-4-methoxy-3,5-diprenyl) phenyl-3-(3- pyridinyl)-propene-1-one (C10) is a potential new anti-leukemia agent. In this study, we investigated the molecular mechanisms of the anti-leukemia effects ofC10on different leukemia cellsin vitro.C10showed strong inhibition of proliferation of the human erythroleukemia cell line HEL and human myeloid leukemia cell line K562, and several cell and flow cytometer assays showed that inhibition byC10was due to the regulation of gene expression or phosphorylation in the apoptosis and autophagy pathways. The results showed thatC10regulated the expression of Bax, c-Myc, Bcl-2, P38/AMPK and ERK 1/2, activated the expression of Caspase-3, -8, and PARP at the protein level in the apoptosis pathway of the two leukemia cell types, and inhibited the expression of erythroleukemia carcinogene Fli-1 in the human erythroleukemia cell line HEL. Additionally,treatment with the compound induced a time-dependent increase in expression of LC 3A/Bviainhibiting the AKT-mTOR pathway, which is associated with cell autophagy. Taken together, the above results suggest that the novel synthesized 3’,5’-diprenylated chalcone can prevent the growth of leukemia cells by inducing apoptosis and autophagy.
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影响因子：
--
作者：
Tamaki H;Harashima N;Hiraki M;Arichi N;Nishimura N;Shiina H;Naora K;Harada M
通讯作者：
Harada M
影响因子：
5.6
作者：
Kłósek M;Mertas A;Król W;Jaworska D;Szymszal J;Szliszka E
通讯作者：
Szliszka E
DOI：
10.1186/1476-069x-10-s1-s8
发表时间：
2011-04-05
期刊：
Environmental health : a global access science source
影响因子：
--
作者：
Terracini B
通讯作者：
Terracini B
影响因子：
--
作者：
Michael V. Fiandalo;N. Kyprianou
通讯作者：
Michael V. Fiandalo;N. Kyprianou
影响因子：
6.7
作者：
Fei Peng;Guangcheng Wang;Xiuxia Li;Dong Cao;Zhuang Yang;Liang Ma;Haoyu Ye;X. Liang;Yan Ran;Jinying Chen;J. Qiu;Caifeng Xie;Chong-yang Deng;Mingli Xiang;A. Peng;Yuquan Wei;Li-juan Chen
通讯作者：
Fei Peng;Guangcheng Wang;Xiuxia Li;Dong Cao;Zhuang Yang;Liang Ma;Haoyu Ye;X. Liang;Yan Ran;Jinying Chen;J. Qiu;Caifeng Xie;Chong-yang Deng;Mingli Xiang;A. Peng;Yuquan Wei;Li-juan Chen