Kukoamine A inhibits human glioblastoma cell growth and migration through apoptosis induction and epithelial-mesenchymal transition attenuation.
Cortex lycii radicis is the dried root bark of Lycium chinense, a traditional Chinese herb used in multiple ailments. The crude extract of Cortex lycii radicis has growth inhibition effect on GBM cells. Kukoamine A (KuA) is a spermine alkaloid derived from it. KuA possesses antioxidant, anti-inflammatory activities, but its anticancer activity is unknown. In this study, the growth and migration inhibition effect of KuA on human GBM cells and the possible mechanism of its activity were investigated. After KuA treatment, proliferation and colony formation of GBM cells were decreased significantly; apoptotic cells were increased; the cell cycle was arrested G0/G1phase; the migration and invasion were decreased, the growth of tumors initiated from GBM cells was inhibited significantly; the expressions of 5-Lipoxygenase (5-LOX) were decreased, apoptotic proteins, Bax and caspase-3 were increased, and antiapoptotic protein Bcl-2 was decreased significantly; The expressions of CCAAT/enhancer binding protein β (C/EBPβ), N-cadherin, vimentin, twist and snail+slug were decreased significantly, while the expression of E-cadherin was increased significantly in KuA treated GBM cells and tumor tissues. KuA inhibited human glioblastoma cell growth and migration in vitro and in vivo through apoptosis induction and epithelial-mesenchymal transition attenuation by downregulating expressions of 5-LOX and C/EBPβ.
Laboratory of Experimental Oncology, State Key Laboratory of Biotherapy/Collaborative Innovation Center for Biotherapy, West China Hospital, West China Clinical Medical School, Sichuan University, Chengdu 610041 China.
Qiaoping
Q
Wang
Laboratory of Experimental Oncology, State Key Laboratory of Biotherapy/Collaborative Innovation Center for Biotherapy, West China Hospital, West China Clinical Medical School, Sichuan University, Chengdu 610041 China.
Haiyan
H
Li
Laboratory of Experimental Oncology, State Key Laboratory of Biotherapy/Collaborative Innovation Center for Biotherapy, West China Hospital, West China Clinical Medical School, Sichuan University, Chengdu 610041 China.
Zhen
Z
Sun
Laboratory of Experimental Oncology, State Key Laboratory of Biotherapy/Collaborative Innovation Center for Biotherapy, West China Hospital, West China Clinical Medical School, Sichuan University, Chengdu 610041 China.
Lihua
L
Dong
Laboratory of Experimental Oncology, State Key Laboratory of Biotherapy/Collaborative Innovation Center for Biotherapy, West China Hospital, West China Clinical Medical School, Sichuan University, Chengdu 610041 China.
Ling
L
Gao
Laboratory of Experimental Oncology, State Key Laboratory of Biotherapy/Collaborative Innovation Center for Biotherapy, West China Hospital, West China Clinical Medical School, Sichuan University, Chengdu 610041 China.
Chunlan
C
Liu
Laboratory of Experimental Oncology, State Key Laboratory of Biotherapy/Collaborative Innovation Center for Biotherapy, West China Hospital, West China Clinical Medical School, Sichuan University, Chengdu 610041 China.
Xiujie
X
Wang
D000818:Animals; D017209:Apoptosis / Q000187:drug effects* / Q000235:genetics; D002465:Cell Movement / Q000187:drug effects* / Q000235:genetics; D058750:Epithelial-Mesenchymal Transition / Q000187:drug effects* / Q000235:genetics; D059585:G1 Phase Cell Cycle Checkpoints / Q000187:drug effects* / Q000235:genetics; D005909:Glioblastoma / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D009361:Neoplasm Invasiveness; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism; D051381:Rats; D013096:Spermine / Q000031:analogs & derivatives* / Q000494:pharmacology
D009363:Neoplasm Proteins; C096274:kukoamine A; D013096:Spermine