School of Chinese Medicine
Chronic myeloid leukemia (CML), an acquired malignant myeloproliferative disorder of hematopoietic stem cells, is one of the three most common forms of leukemia. In this study, we investigated the effects of bruceine D, which have been isolated from Brucea javanica (L.) Merr. on human chronic myeloid leukemia K562 cells. MTT assay was used to evaluate cell growth inhibition. Flow cytometry was performed to analyze mitochondrial membrane potential (ΔΨm). Western blot was applied to detect expression of cytochrome c, caspases-9, -3, PARP and other proteins. Bruceine D exhibited potent cytotoxicity to K562 cells with IC50 of 6.37 ± 0.39 μM. It led to loss of ΔΨm, release of cytochrome c, activation of caspases-9, -3 and cleavage of PARP, which suggested that bruceine D induced apoptosis of K562 cells through mitochondrial pathway. In addition, bruceine D inhibited the phosphorylation of AKT and ERK. It’s indicative that the potent anticancer activity of bruceine D be related to MAPK and PI3K pathways.
Bruceine D, apoptosis, mitochondrial pathway, AKT, ERK, phosphorylation
Source Publication Title
American Journal of Cancer Research
Creative Commons Attribution Noncommercial License
The work was supported by the Faculty Research Grant of Hong Kong Baptist University (FRG2/13-14/044), National Natural Science Foundation of China (No. 81473320), the Fund from Guangdong Science and Technology Department & Guangdong Academy of Traditional Chinese Medicine (2016A020226024), the Science Fund of the Education Bureau of Guangzhou City (1201410039) and Fund of Guangdong Education Department (2015KTSCX112).
Link to Publisher's Edition
Zhang, Jian-Ye, Min-Ting Lin, Ho-Yi Tung, Si-Li Tang, Tao Yi, Ya-Zhou Zhang, Yi-Na Tang, Zhong-Zhen Zhen, and Hu-Biao Chen. "Bruceine D induces apoptosis in human chronic myeloid leukemia K562 cells via mitochondrial pathway." American Journal of Cancer Research 6.4 (2016): 819-826.