Artesunate induces apoptosis and inhibits the proliferation, stemness, and tumorigenesis of leukemia

青蒿琥酯诱导细胞凋亡并抑制白血病的增殖、干细胞形成和肿瘤发生

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作者:Shengmei Chen, Silin Gan, Lijie Han, Xue Li, Xiaoqing Xie, Dianbin Zou, Hui Sun

Background

Leukemia is characterized by the presence of highly malignant tumors formed in the hematopoietic system. Artesunate (Art), a semi-synthetic derivative of artemisinin, is commonly used as an antimalarial drug and has been proven to possess anticancer potential.

Conclusions

Our present study provides new insights into the mechanisms of Art's anticancer potential in leukemia.

Methods

In this study, the effect of Art on the proliferation and stemness of human acute promyelocyte leukemia HL-60 cells and acute myeloid leukemia KG1a cells was investigated. Flow cytometry, colony formation assay, the protein expressive levels of survivin, P21, cleaved caspase 3, Bax, Bcl-2, Ki67 were detected the effect of Art on HL-60 and KG1a cells proliferation and apoptosis. At the same time, cell sphere formation assay and the protein expressive levels of CD44, SOX2, ALDH1 and OCT4 were used to analyze the effects of Art on cancer stem cell-like property in vitro. The orthotopic xenograft mouse models were established by using KG1a cells in BALB/c athymic nude mice. Tumor weigh was detected. The protein levels of survivin and Ki67 were detected by immunohistochemistry assays.

Results

Art induced cell apoptosis and inhibited cell proliferation and stemness in a dose-dependent manner. In the meantime, the results exhibited that Art inhibited the growth and stemness of transplanted tumors via the suppression of the MEK/ERK and PI3K/Akt pathway. Conclusions: Our present study provides new insights into the mechanisms of Art's anticancer potential in leukemia.

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