1.Seed oil of Brucea javanica induces apoptosis through the PI3K/Akt signaling pathway in acute lymphocytic leukemia Jurkat cells.
Hong ZHANG ; Shi-Liang YIN ; Li-Hui WANG ; Li-Na JIA ; Guang-Yue SU ; Xiao-Qing LIU ; Fan ZHOU ; Peter BRESLIN ; Ran MENG ; Qi-Yi LI ; Jing-Yu YANG ; Chun-Fu WU
Chinese Journal of Natural Medicines (English Ed.) 2021;19(8):608-620
Brucea javanica oil emulsion (BJOE) has been used to treat tumor in China for more than 40 years. However, its components and effectiveness in the treatment of acute lymphocytic leukemia (ALL) and its mechanism of anti-cancer activity remain unknown. In the current study, high-performance liquid chromatography-evaporative light scattering detector (HPLC-ELSD) was used to analyze the components of BJOE. Then, the anti-leukemia effects of BJOE were examined both in vitro and in vivo using ALL Jurkat cells and the p388 mouse leukemia transplant model, respectively. The primary ALL leukemia cells were also used to confirm the anti-leukemia effects of BJOE. The apoptotic-related results indicated that BJOE induced apoptosis in Jurkat cells and were suggestive of intrinsic apoptotic induction. Moreover, BJOE inhibited Akt (protein kinase B) activation and upregulated its downstream targets p53 and FoxO1 (forkhead box gene, group O-1) to initiate apoptosis. The activation of GSK3β was also involved. Our findings demonstrate that BJOE has anti-leukemia effects on ALL cells and can induce apoptosis in Jurkat cells through the phosphoinositide3-kinase (PI3K) /Akt signaling pathway.
Animals
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Apoptosis
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Brucea/chemistry*
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Glycogen Synthase Kinase 3
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Humans
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Jurkat Cells
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Mice
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Phosphatidylinositol 3-Kinases/genetics*
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Plant Oils/pharmacology*
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Precursor Cell Lymphoblastic Leukemia-Lymphoma/drug therapy*
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Proto-Oncogene Proteins c-akt/genetics*
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Seeds/chemistry*
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Signal Transduction