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Cytotoxic Components from the leaves of Erythrophleum fordii Induce Human Acute Leukemia Cell Apoptosis through Caspase 3 Activation and PARP Cleavage
Bioorganic & Medicinal Chemistry Letters ( IF 2.7 ) Pub Date : 2020-11-05 , DOI: 10.1016/j.bmcl.2020.127673
Phuong Hien Thi Vo 1 , Thuy Duong Thi Nguyen 2 , Hoa Thanh Tran 2 , Yen Nhi Nguyen 1 , Minh Thu Doan 2 , Phi Hung Nguyen 3 , Giang Thi Kim Lien 4 , Dao Cuong To 5 , Manh Hung Tran 1
Affiliation  

Cassaine diterpenoids as erythrofordins A-C (1-3), pseudo-erythrosuamin (4), and erythrofordin U (5) isolated from the leaves of Vietnamese Erythrophleum fordii Oliver were tested cytotoxic activity against human leukemia cancer cells. The results showed that these metabolites exhibited dose-dependent cytotoxicity against human leukemia HL-60 and KG cells with IC50 values ranging from 15.2 ±1.5 to 42.2 ±3.6 µM. Treatment with erythrofordin B led to the apoptosis of HL-60 and KG cells due to the activation of caspase 3, caspase 9, and poly (ADP-ribose) polymerase (PARP). Erythrofordin B significantly increased Bak protein expression, but downregulated the anti-apoptotic protein Bcl-2, in HL-60 cells. In silico results demonstrated that erythrofordin B can bind to both the procaspase-3 allosteric site and the PARP-1 active site, with binding energies of -7.36 and -10.76 kcal/mol, respectively. These results indicated that the leaves of Vietnamese E. fordii, which contain cassaine diterpenoids, can induce the apoptosis of human leukemia cancer cells.



中文翻译:

从叶细胞毒性组件格木诱导人急性白血病细胞凋亡通过胱天蛋白酶3激活和PARP切割

测试了从越南红ry叶中分离得到的酪蛋白二萜类化合物,如erythrofordins AC(1-3),pseudo-erythrosuamin(4)和erythrofordin U(5)。结果表明,这些代谢物对人白血病HL-60和KG细胞表现出剂量依赖性的细胞毒性,IC 50 值为15.2±1.5至42.2±3.6 µM。由于胱天蛋白酶3,胱天蛋白酶9和聚(ADP-核糖)聚合酶(PARP)的激活,用促红细胞生成素B处理导致HL-60和KG细胞凋亡。促红细胞生成素B在HL-60细胞中显着增加Bak蛋白的表达,但下调抗凋亡蛋白Bcl-2的表达。电脑分析结果表明,促红细胞生成素B可以结合procaspase-3变构位点和PARP-1活性位点,结合能分别为-7.36和-10.76 kcal / mol。这些结果表明,含有大麦碱二萜类化合物的越南大肠埃希氏菌的叶子可以诱导人白血病癌细胞的凋亡。

更新日期:2020-11-06
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