Matrine induces apoptosis in human acute myeloid leukemia cells via the mitochondrial pathway and Akt inactivation.
Matrine induces apoptosis in human acute myeloid leukemia cells via the mitochondrial pathway and Akt inactivation.
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苦参碱通过线粒体途径和 Akt 失活诱导人急性髓系白血病细胞凋亡
DOI：
10.1371/journal.pone.0046853
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Han Y
中科院分区：
文献类型：
--
作者：
Zhang S;Zhang Y;Zhuang Y;Wang J;Ye J;Zhang S;Wu J;Yu K;Han Y
急性髓性白血病（AML）是一种血液恶性肿瘤，其特征是骨髓中未成熟髓细胞数量迅速增加。尽管最近在治疗方面取得了进展，但AML仍然是一种不治之症。苦参碱是从苦参中提取的主要成分，已被证明对多种癌细胞系具有抗癌作用。然而，苦参碱对AML的作用在很大程度上仍然未知。在这里，我们研究了其在体外和体内对人AML细胞的抗癌作用和潜在机制。结果表明，苦参碱以剂量和时间依赖性方式抑制AML细胞系以及AML患者的原代AML细胞的细胞活力并诱导细胞凋亡。苦参碱通过破坏线粒体膜电位、诱导线粒体释放细胞色素c、降低Bcl-2/Bax比值、增加caspase-3活化、降低p-Akt和p-ERK 1/2水平诱导细胞凋亡。caspase-3抑制剂Z-DEVD-FMK和PI 3 K/Akt激活剂IGF-1可部分阻断苦参碱诱导AML细胞凋亡的作用。苦参碱有效地抑制皮下接种HL-60细胞在SCID小鼠体内的肿瘤生长。这些结果表明苦参碱能抑制AML细胞增殖并诱导其凋亡，可能成为一种新的有效的AML化疗药物。
Acute myeloid leukemia (AML) is a hematological malignancy characterized by a rapid increase in the number of immature myeloid cells in bone marrow. Despite recent advances in the treatment, AML remains an incurable disease. Matrine, a major component extracted from Sophora flavescens Ait, has been demonstrated to exert anticancer effects on various cancer cell lines. However, the effects of matrine on AML remain largely unknown. Here we investigated its anticancer effects and underlying mechanisms on human AML cells in vitro and in vivo. The results showed that matrine inhibited cell viability and induced cell apoptosis in AML cell lines as well as primary AML cells from patients with AML in a dose- and time-dependent manner. Matrine induced apoptosis by collapsing the mitochondrial membrane potential, inducing cytochrome c release from mitochondria, reducing the ratio of Bcl-2/Bax, increasing activation of caspase-3, and decreasing the levels of p-Akt and p-ERK1/2. The apoptotic effects of matrine on AML cells were partially blocked by a caspase-3 inhibitor Z-DEVD-FMK and a PI3K/Akt activator IGF-1, respectively. Matrine potently inhibited in vivo tumor growth following subcutaneous inoculation of HL-60 cells in SCID mice. These findings indicate that matrine can inhibit cell proliferation and induce apoptosis of AML cells and may be a novel effective candidate as chemotherapeutic agent against AML.
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影响因子：
3.7
作者：
Merhi F;Tang R;Piedfer M;Mathieu J;Bombarda I;Zaher M;Kolb JP;Billard C;Bauvois B
通讯作者：
Bauvois B
影响因子：
5.4
作者：
Dai, Zhi-jun;Gao, Jie;Guan, Hai-tao
通讯作者：
Guan, Hai-tao
影响因子：
4.3
作者：
Zhang, Jun-Qiang;Li, Yu-Min;Ren, Zhi-Jian
通讯作者：
Ren, Zhi-Jian
苦参碱在体外和体内抑制胰腺癌细胞增殖并诱导其凋亡
影响因子：
2
作者：
Liu, Tianyou;Song, Yon;Sun, Xueying
通讯作者：
Sun, Xueying
影响因子：
9.3
作者：
Cheng, H;Xia, B;Guo, QS
通讯作者：
Guo, QS