title: Bruceine D induces apoptosis in human chronic myeloid leukemia K562 cells via mitochondrial pathway.
abstract: 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.
authors.affiliation: School of Chinese Medicine, Hong Kong Baptist UniversityKowloon Tong, Kowloon, Hong Kong, The People's Republic of China; School of Pharmaceutical Sciences, Guangzhou Medical University195 Dongfeng Road West, Guangzhou, Guangdong, The People's Republic of China.
authors.forename: Jian-Ye
authors.initials: JY
authors.lastname: Zhang
authors.affiliation: School of Pharmaceutical Sciences, Guangzhou Medical University 195 Dongfeng Road West, Guangzhou, Guangdong, The People's Republic of China.
authors.forename: Min-Ting
authors.initials: MT
authors.lastname: Lin
authors.affiliation: School of Chinese Medicine, Hong Kong Baptist University Kowloon Tong, Kowloon, Hong Kong, The People's Republic of China.
authors.forename: Ho-Yi
authors.initials: HY
authors.lastname: Tung
authors.affiliation: School of Pharmaceutical Sciences, Guangzhou Medical University 195 Dongfeng Road West, Guangzhou, Guangdong, The People's Republic of China.
authors.forename: Si-Li
authors.initials: SL
authors.lastname: Tang
authors.affiliation: School of Chinese Medicine, Hong Kong Baptist University Kowloon Tong, Kowloon, Hong Kong, The People's Republic of China.
authors.forename: Tao
authors.initials: T
authors.lastname: Yi
authors.affiliation: School of Chinese Medicine, Hong Kong Baptist University Kowloon Tong, Kowloon, Hong Kong, The People's Republic of China.
authors.forename: Ya-Zhou
authors.initials: YZ
authors.lastname: Zhang
authors.affiliation: School of Chinese Medicine, Hong Kong Baptist University Kowloon Tong, Kowloon, Hong Kong, The People's Republic of China.
authors.forename: Yi-Na
authors.initials: YN
authors.lastname: Tang
authors.affiliation: School of Chinese Medicine, Hong Kong Baptist University Kowloon Tong, Kowloon, Hong Kong, The People's Republic of China.
authors.forename: Zhong-Zhen
authors.initials: ZZ
authors.lastname: Zhao
authors.affiliation: School of Chinese Medicine, Hong Kong Baptist University Kowloon Tong, Kowloon, Hong Kong, The People's Republic of China.
authors.forename: Hu-Biao
authors.initials: HB
authors.lastname: Chen
keywords: AKT; Bruceine D; ERK; apoptosis; mitochondrial pathway; phosphorylation