TY - JOUR
T1 - Bruceine D induces apoptosis in human chronic myeloid leukemia K562 cells via mitochondrial pathway
AU - Zhang, Jian-Ye
AU - Lin, Min-Ting
AU - Tung, Ho-Yi
AU - Tang, Si-Li
AU - Yi, Tao
AU - Zhang, Ya-Zhou
AU - Tang, Yi-Na
AU - Zhao, Zhong-Zhen
AU - Chen, Hu-Biao
N1 - Funding Information:
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 Guangexpression zhou City (1201410039) and Fund of Guangdong Education Department (2015KTSCX112).
PY - 2016/4
Y1 - 2016/4
N2 - 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.
AB - 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.
KW - AKT
KW - Apoptosis
KW - Bruceine D
KW - ERK
KW - Mitochondrial pathway
KW - Phosphorylation
UR - http://www.scopus.com/inward/record.url?scp=84991518526&partnerID=8YFLogxK
M3 - Journal article
AN - SCOPUS:84991518526
SN - 2156-6976
VL - 6
SP - 819
EP - 826
JO - American Journal of Cancer Research
JF - American Journal of Cancer Research
IS - 4
ER -
